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Nothing went right for the San Francisco 49ers the last time they met the Philadelphia Eagles in the postseason. Head coach Kyle Shanahan, quarterback Brock Purdy and company hope things go in their favor this time around.

The sixth-seeded 49ers (12-5) and No. 3 Eagles (11-6) square off in the playoffs for the second time in four years when they collide in Philadelphia at 4:30 p.m. ET on Sunday during Wild Card Weekend. Lincoln Financial Field proved to be a house of horrors for San Francisco in the 2022 NFC Championship Game as then-rookie Brock Purdy tore the ulnar collateral ligament in his right elbow during the team's first offensive series and backup Josh Johnson suffered a concussion early in the third quarter, forcing the 262nd and final pick of the 2022 NFL Draft back under center.

Purdy attempted just two passes upon his return, completing both for a total of 4 yards, and finished 4-of-4 for 23 yards as the 49ers suffered a 31-7 loss. The 26-year-old quarterback missed nine games this season with shoulder and toe injuries but played in San Francisco's final seven contests, leading the team to victory in the first six before its 13-3 loss to the top-seeded Seattle Seahawks in the season finale.

Defending Super Bowl champion Philadelphia also enters the matchup on the heels of a setback, as it dropped a 24-17 decision to the Washington Commanders in Week 18 for its fourth loss in seven games. Even though they were somewhat of an enigma, the Eagles had a double-digit win total for the fourth consecutive season and were one of only four teams with a pair of 1,000-yard receivers (DeVonta Smith, 1,008 and A.J. Brown, 1,003).

The Eagles are 5.5-point favorites and the Over/Under for total points scored is 44.5 in the latest DraftKings NFL odds for San Francisco vs. Philadelphia in the NFL Wild Card Round.

Here is a look at the 49ers vs. Eagles matchup from a betting perspective: 

49ers vs. Eagles odds

  • Opening spread: Eagles -3.5
  • Opening money line: Eagles -192, 49ers +160
  • Opening total: 46.5

This line opened at 3.5 points at DraftKings but has risen to 5.5. The reason could be the fact that San Francisco's Dee Winters (ankle) has yet to participate in practice this week. Winters, who led the team with 67 solo and 101 total tackles, and fellow linebacker Tatum Bethune (groin) both were injured in the regular-season finale. Bethune is done for the year, but 12-time Pro Bowl left tackle Trent Williams was a limited participant in Thursday's practice after missing Week 18 with a hamstring injury.

Another factor could be the potential return of Eagles tackle Lane Johnson, a six-time Pro Bowler who practiced in limited fashion Tuesday for the first time since going down with a foot injury against the Detroit Lions in Week 11.

Meanwhile, the total for this showdown has dropped, as it currently is at 44.5 after opening at 46.5.

49ers betting profile

  • Opening win total: 10.5 wins  
  • W/L record: 12-5
  • ATS record: 11-6
  • O/U record: 10-7

Covering the spread has been a problem for the 49ers of late, as they failed to do so in both of their last two contests after having accomplished the feat in five straight. San Francisco outslugged the Chicago Bears 42-38 in Week 17 but was favored by 4.5 points and was getting 2.5 in its 10-point loss to Seattle in the finale.

The 49ers will need a better effort from their offense than the one they received against the Seahawks. San Francisco racked up only 173 total yards versus Seattle, with Purdy throwing for just 127 with no touchdowns while Christian McCaffrey gained 23 yards on eight carries. Those totals were season lows for both players.

McCaffrey has fared well against the Eagles as a member of the 49ers. The 29-year-old ran for 84 yards and a touchdown in the 2022 NFC Championship Game and recorded 93 yards and a score in Week 13 of the 2023 season en route to the league rushing title (1,459 yards) and NFL Offensive Player of the Year honors.

Another productive outing could be in store for McCaffrey on Sunday as Philadelphia was 22nd in the league -- and 12th among the 14 playoff teams -- against the run this season with an average of 124.4 yards allowed on the ground.

Eagles betting profile

  • Opening win total: 10.5 wins  
  • W/L record: 11-6
  • ATS record: 10-7 
  • O/U record: 7-10

The Eagles had their run of three consecutive covers halted with their loss to the Commanders as 3.5 favorites in the season finale. That should be taken with a grain of salt, however, as Brown, Jalen Hurts, Saquon Barkley and Dallas Goedert all sat out.

Goedert was dealing with a knee injury and is questionable for Sunday's wild card game. But the other three certainly will be on the field against San Francisco, which didn't fare well against the spread as an underdog this season. The 49ers went 2-4 ATS overall and 1-2 on the road as underdogs in 2025, which also may be playing a role in the increase of the spread for this matchup.

Despite losing 42-19 to San Francisco at home in 2023, Philadelphia received some big offensive performances. Hurts threw for 298 yards and a touchdown while also running for a score, Brown hauled in eight passes for 114 yards and Smith had nine receptions for 96 yards and a TD.

Seven of the Eagles' 11 regular-season victories were by six or more points, and their defense could give Purdy and San Francisco's aerial attack fits on Sunday. Philadelphia allowed an average of 189.8 passing yards per game this year, ranking eighth in the NFL and fifth among the 14 teams participating in the playoffs.

49ers-Eagles prop pick

Christian McCaffrey Under 44.5 receiving yards (-111): As mentioned above, Philadelphia defends the pass well, and Shanahan likely will have McCaffrey concentrating much more on running the football, especially since he eclipsed the 1,000-yard mark (1,202) for the fifth time in his nine-year career this season. McCaffrey hasn't been a big factor in the passing game of late anyway, as he has finished with fewer than 45 receiving yards in six of his last seven games after registering at least 52 in all but one of his first 10 contests this campaign.