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The 'Monday Night Football' matchup between the Colts and 49ers at 8:15 p.m. ET features the top two Fantasy running backs in the NFL DFS player pool. Jonathan Taylor and Christian McCaffrey rank first and second, respectively, in positional Fantasy points as they'll be the first names that come to mind when making NFL DFS picks. Both teams have stud tight ends as well in Tyler Warren and George Kittle, but the differing abilities of their respective quarterbacks shouldn't be overlooked when crafting a MNF DFS strategy.

Brock Purdy boosts the value of wideouts like Jauan Jennings, while one can't necessarily say that of Philip Rivers with Colts receivers. The limitations of the 44-year-old should make you give a little extra thought to if the likes of Alec Pierce or Michael Pittman Jr. should find their way into your NFL DFS lineups. Before making any 49ers vs. Colts NFL DFS picks on sites like FanDuel or DraftKings for 'Monday Night Football,' be sure to check out the NFL DFS advice, strategy, and stacks from SportsLine daily Fantasy expert Mike McClure. 

McClure is a legendary professional DFS player with more than $2 million in career winnings. He uses a powerful prediction model that simulates every snap of NFL action, taking factors such as matchups, statistical trends, and injuries into account. This allows him to find the best DFS values that he shares only with members at SportsLine. His methodology has led to enormous cashes on FanDuel and DraftKings, including. In 2023, he finished tied for first in the DraftKings Millionaire Maker twice and the FanDuel Million once. Anyone who has followed him could be way up.

Now, McClure has turned his attention to the 'Monday Night Football' DFS slate and just locked in his top daily Fantasy football picks. You can only see his picks and analysis at SportsLine. 

Top NFL DFS picks for 49ers vs. Colts

One of McClure's top NFL DFS picks for 'Monday Night Football' is Niners running back Christian McCaffrey, who has an over/under of 62.5 rushing yards. The three-time Pro Bowler is as consistent a Fantasy player there is, and he's coming off a game with 87 scrimmage yards and a touchdown. He has at least 96 total yards or a touchdown in all but one game this season as both his running and receiving ability give him an extremely high Fantasy floor. McCaffrey is averaging a touchdown per game this year and is on pace for 2,115 scrimmage yards, which would be the sixth-most by any player over the last decade. See who else to roster at SportsLine. 

Bet McCaffrey to go Over 62.5 rushing yards at DraftKings, where new users can target the DraftKings promo code, which offers $200 in bonus bets if your bet wins:

McClure is also rostering Colts tight end Tyler Warren, who ranks fourth amongst tight ends in receiving yards (718) and is sixth in positional Fantasy points as a rookie. He's been targeted six times in each of the last two weeks, so he's remained a big part of Indy's offensive game plan even after Daniel Jones' injury. That should especially be the case on Monday as San Francisco has had no answer for tight ends in the red zone recently. The Niners have allowed six touchdowns to tight ends over their last six games as one can expect Indy to target that defensive weakness. See who else to roster at SportsLine. 

Bet Warren to go Over 34.5 receiving yards at DraftKings:

How to set 49ers vs. Colts NFL DFS lineups

McClure is targeting another undervalued player who could explode for huge numbers on 'Monday Night Football.' This pick could be the difference between winning your tournaments and cash games or going home with nothing. You can only see who it is, and the rest of McClure's NFL DFS picks, at SportsLine.

So who is Mike McClure including in his optimal NFL DFS lineups for 'Monday Night Football', and which under-the-radar player offers huge value? Visit SportsLine now to see optimal NFL DFS picks, NFL DFS rankings, NFL DFS advice and NFL DFS stacks, all from a daily Fantasy expert with more than $2 million in winnings, and find out.