RENTON, Wash. – The Seattle Seahawks will have running back Ken Walker III for their Monday night game against the Detroit Lions, but will be without at least four key players on defense.

Seattle ruled out defensive linemen Leonard Williams and Byron Murphy and outside linebackers Uchenna Nwosu and Boye Mafe on Saturday. Inside linebacker Jerome Baker is questionable.

All are starters except Murphy, a first-round pick who played a total of 78 snaps in his first two NFL games before suffering a hamstring injury in Seattle's win over the Miami Dolphins last week.

Williams, the highest-paid defensive player in Seahawks history, suffered a rib injury in that game. Mafe, who ranks sixth among edge defenders in pass-block win rate this season, previously suffered a knee injury against Miami. Nwosu, Seattle's top defender, missed the first three games with an MCL sprain.

According to ESPN BET, the Lions (2-1) were 3.5-point favorites as of Saturday afternoon.

The Seahawks' 3-0 start comes with the caveat that they beat the Denver Broncos in Bo Nix's NFL debut, the New England Patriots in overtime and the Tua Tagovailoa-less Dolphins. The game against the Lions at Ford Field was already considered their first real challenge of the season, and now they will be without arguably their four best front-seven defensemen as they look to go 4-0 under new coach Mike Macdonald .

“Four guys are down, four more are going to step up,” Macdonald said. “I’m looking forward to seeing these guys play. When you talk about having depth on your football team, you want to feel like, 'Okay, I can't wait to see who gets this opportunity now.' So that's our opinion. The boys will have more opportunities than usual and we look forward to seeing what they do.”

Macdonald acknowledged that playing in three games in 10 days was a factor in some of the decisions Seattle has made regarding who will and won't play on Monday night.

“It’s definitely a point of discussion,” he said. “It’s still early in the season. So if we were playing in the Super Bowl, the conversation would probably be different.”

Walker missed the last two games due to an oblique injury he suffered in the fourth quarter of the opening game. The Seahawks listed him as a limited player on Thursday and Friday and as a full player on Saturday. They also practiced on Wednesday but were not required to release an injury report that day.

“He looked good,” Macdonald said of Walker. “He’s ready to go.”

Baker was limited on Saturday after not practicing on Thursday or Friday.

Macdonald said Mafe's knee injury was “nothing serious”. A source told ESPN that Murphy, the 16th overall pick in April's draft, may be sidelined for more than a week.

“I'm not sure about the actual timeline,” Macdonald said, referring to injuries to Mafe, Murphy, Williams and Nwosu, “but none of them are long-term, I don't think, unless something changes. “

Nwosu went down in the final preseason game. The Seahawks did not place him on injured reserve — which would have meant he would have missed at least the first four games — because they believed he could return in Week 4. Macdonald said Nwosu suffered no setback.

“You know Uchenna,” he said. “This guy works extremely hard. It was worth a try and then having him do all the stuff on the field, some of the walk-throughs and so on, staying committed, I think it was the right decision, even if it wasn't “It didn't work out in our favor.”

Right-back Anthony Bradford was a full participant on Friday and Saturday after not training on Thursday. He started the first three games but committed six penalties. Seattle worked third-round rookie Christian Haynes at right guard in each of the first two games. Macdonald said both will play Monday night.