Week 6 Start 'Em, Sit 'Em Advice for Difficult Fantasy Football Lineup Decisions

Week 6 of the NFL season got underway on Thursday night with an NFC East battle between the Philadelphia Eagles and New York Giants. With 14 games left on the schedule, managers may face more than a few tough fantasy decisions.

The 2025 season has been tough on the injury front, and bye weeks have further diluted the available player pool. Few managers have the luxury of leaning solely on stars while avoiding difficult matchups.

Here, we'll dig into a few of the tougher remaining lineup decisions of Week 6. As a reminder, the Houston Texans and Minnesota Vikings are out of action this week.

Start: James Cook, RB, Buffalo Bills

AP Photo/Jeffrey T. Barnes

The Buffalo Bills suffered their first loss of the season in Week 5, and they're now heading toward a Monday night road matchup with the Atlanta Falcons. That may concern James Cook managers because of Atlanta's defense.

No team has surrendered fewer fantasy points to opposing running backs than the Falcons this season.

While the matchup certainly isn't ideal, managers should trust Cook's point-per-reception (PPR) value to provide a solid floor. While he didn't catch a pass on Sunday, Cook averaged four targets and three receptions over the first four weeks of the season.

Cook has also averaged over 100 scrimmage yards and a touchdown per game in 2025. While last week's 49-yard outing and this week's matchup are concerning, Cook deserves to stay in starting lineups.

Sit: Alvin Kamara, RB, New Orleans Saints

AP Photo/Gerald Herbert

Alvin Kamara's PPR floor makes him a justifiable starter in deeper leagues. However, managers should look for alternatives and avoid Kamara this week if possible.

While the 30-year-old has averaged just over three receptions per game, he's also averaged just 72 scrimmage yards and has found the end zone only once. He's tallied fewer than 60 scrimmage yards in three of his five outings.

The problem for Kamara managers is the emergence of Kendre Miller, who actually recorded more carries than Kamara in Week 5. The split nature of New Orleans' backfield makes Kamara a matchup-based play moving forward.

And the New England Patriots are not a good matchup for the Saints. New England has surrendered the fifth-fewest fantasy points to opposing running backs.

Start: Keenan Allen, WR, Los Angeles Chargers

AP Photo/Adam Hunger

Managers may be wary of Los Angeles Chargers wide receiver Keenan Allen for a couple of reasons this week. For one, L.A.'s three-headed receiving attack has made it difficult to predict which receiver—Allen, Quentin Johnston or Ladd McConkey—will shine brightest.

Secondly, the Miami Dolphins have surrendered the seventh-fewest fantasy points to opposing wide receivers.

Of course, Miami hasn't allowed many fantasy points to receivers because its run defense is bad. The Dolphins aren't actually good at defending the pass and rank 29th in net yards per pass completion allowed.

With Najee Harris and Omarion Hampton both on injured reserve, L.A. should take a pass-heavy approach in Miami. That bodes well for Allen, who leads the Chargers in both targets (44) and receptions (29) this season.

Sit: Jameson Williams, WR, Detroit Lions

AP Photo/Rey Del Rio

Detroit Lions wide receiver Jameson Williams was a breakout fantasy star in 2024, finishing with 58 catches, 1,001 yards and seven touchdowns. Through five weeks this season, he's been a lot more hit-and-miss and has been totally reliant on big plays.

In Week 2, for example, Williams caught just two passes but went for 108 yards and a touchdown. Last week, he caught a single nine-yard pass.

As the Lions have started to find a groove on the ground, Williams has become less of a focal point. He hasn't seen more than two catches in a game since the opener against Green Bay.

While the Jacksonville Jaguars were able to poke some holes in the Kansas City Chiefs' defense last Monday, Kansas City has been solid against opposing wideouts. The Chiefs have surrendered the eighth-fewest fantasy points to opposing WRs and are likely to provide a tough test in Kansas City on Sunday night.

*Fantasy scoring information from FantasyPros.