Saquon Barkley suffered a high-ankle sprain that will keep him out 4-to-8 weeks, and the Giants fear his return could be on the longer side of that timeline. That means Fantasy players need to consider the possibility they will be without Barkley through the team's Week 11 bye.

This obviously has significant ramifications for the Giants, as well as for Fantasy players. The Giants got a terrific performance from rookie Daniel Jones in his NFL debut Sunday, a win over the Buccaneers, but he'll now be without the team's best offensive player as he tries to build on that. Fantasy players, meanwhile, will need to replace their first-round pick for at least the next month, if not longer.

The Giants' offense could be in trouble without Barkley, although with Jones in place, Sterling Shepard healthy, Evan Engram making plays, and Golden Tate ready to return from his suspension in Week 5, they may not be a disaster. However, the loss of Barkley is obviously a huge one for Fantasy players, one you'll have a tough time making up for.

Your best bet isn't going to come on the waiver wire this week. There just isn't that kind of impact potential available right now. Wayne Gallman figures to replace Barkley for the Giants, but he's never shown the ability to be a difference maker, and this isn't the kind of offense that is going to elevate him much.

However, if you are limited to waiver-wire options, your top choice should probably be Rex Burkhead (47%). He took advantage of James White's absence to dominate playing time for the Patriots in Week 3, and while he won't see that kind of workload moving forward, he does have at least seven touches in each game, including 13-plus in two of three. With Sony Michel looking like a no-dimensional player so far, maybe Burkhead can carve out a role in both facets of the game that keeps him Fantasy relevant.

You could also consider Darrel Williams (2%), who played a significant role with Damien Williams sidelined in Week 3; Ronald Jones (46%), who has outplayed Peyton Barber in two of three games; or Alexander Mattison, who had 12 carries for 58 yards and a touchdown in Week 3, and should get some work whenever the Vikings are playing from ahead.

If Jones becomes the lead back and the Buccaneers keep clicking like they have the last two weeks, there's some upside there, and Mattison figures to be a potential stud if anything happens to Dalvin Cook. However, if you need an immediate starter, Burkhead looks like the best bet, albeit not one with a ton of upside on a team that doesn't figure to ever give him 15-plus touches.

(I would also consider Rashaad Penny, who missed Week 3 with a hamstring injury, but might have been one of Sunday's biggest winners, as Chris Carson continued to struggle with fumbles. Carson was out-snapped by C.J. Prosise Sunday, and Penny rushed for 61 yards on 10 carries with a touchdown in Week 2. If you are in one of the 22% of CBS Fantasy leagues where Penny is currently available, make him a priority, whether you lost Barkley or not.)

If you really want to find a potential difference maker, it's going to have to come through the trade route. And the perfect target is probably someone who came into the season with big expectations and hasn't lived up to them. Here are four potential targets to consider:

Buy-Low RB Targets
HOU Houston • #28
Age: 28 • Experience: 8 yrs.
YTD Stats
RUYDS
88
REC
7
REYDS
51
TD
1
FPTS/G
8.3
I was wary of Mixon coming into the season as a first-rounder because I was concerned about the state of the Bengals' offense, but I don't think this start is indicative of much of anything. He suffered an ankle injury in Week 1 and was clearly not at full strength in Week 2. He looked a bit better Sunday, and unsurprisingly put together his best performance of the season. Expect more of that moving forward, and with the Bengals showing a bit more spark on offense than expected — 925 passing yards through three games without A.J. Green — Mixon makes for a perfect buy-low candidate.
BAL Baltimore • #34
Age: 32 • Experience: 9 yrs.
YTD Stats
RUYDS
129
REC
9
REYDS
61
TD
0
FPTS/G
7.7
Freeman has four targets in each game and rushed for a season-best 88 yards on 16 carries in Week 3. He hasn't looked great, admittedly, but the Falcons also haven't had a truly huge offensive performance yet, and that is reflected in Freeman's lack of touchdowns. If Ito Smith's concussion keeps him out moving forward, Freeman figures to dominate touches, and better days are ahead overall.
ATL Atlanta • #21
Age: 30 • Experience: 7 yrs.
YTD Stats
RUYDS
203
REC
4
REYDS
8
TD
1
FPTS/G
9.7
The rushing attempts have been there for Gurley, but he has just one touchdown on 44 carries. That will improve moving forward, as Malcolm Brown's red-zone work in Week 1 looks to have been a fluke. The bigger question for Gurley — besides his health, which looks fine for now — is the passing game work. He has just six targets, after racking up 80-plus in the previous two seasons. If that turns around, there's still plenty of upside here.
BUF Buffalo • #5
Age: 29 • Experience: 7 yrs.
YTD Stats
RUYDS
179
REC
14
REYDS
94
TD
0
FPTS/G
12
We've seen a best-case scenario for Fournette through three weeks in terms of touches, as he has a whopping 43 carries and 14 catches. The problem is, he has yet to find the end zone, and hasn't been super efficient overall. Fournette is a boom-or-bust kind of player, and the amount of touches he's getting so far means we should expect more boom than we've gotten so far.