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

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

All are starters except for Murphy, a first-round pick who played 78 combined snaps over his first two NFL games before injuring his hamstring last week in Seattle’s win over the Miami Dolphins.

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

The Lions (2-1) were 3.5-point favorites as of Saturday afternoon, per ESPN BET.

The Seahawks’ 3-0 start has come with the caveat that they’ve beaten the Denver Broncos in Bo Nix’s NFL debut, the New England Patriots in overtime and the Dolphins without Tua Tagovailoa. Playing the Lions at Ford Field already was billed as their first real challenge of the season, and now they’ll be without arguably their four best front-seven defenders as they look to go 4-0 under new coach Mike Macdonald.

“You’ve got four guys that are down, four more guys are going to be up,” Macdonald said. “Looking forward to seeing those guys play. When you talk about having depth on your football team, you want the feeling to be like, ‘OK, I can’t wait to see whoever’s going to get that opportunity now.’ So that’s our view. Guys are going have more opportunities than they’ve usually had, and [we’re] looking forward to seeing what they do.”

Macdonald acknowledged that playing three games in the span of 10 days was a factor on some of the decisions Seattle made with regard to who will and won’t play Monday night.

“It’s definitely a discussion point,” he said. “It’s early in the season, so if we’re playing in the Super Bowl, then it would be a different conversation probably.”

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

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

Baker was limited Saturday after not practicing Thursday or Friday.

Macdonald said Mafe’s knee injury is “nothing major.” A source told ESPN that Murphy, the 16th overall pick in April’s draft, might have to miss more than one week.

“Not sure on actual timelines,” Macdonald said, referring to the Mafe, Murphy, Williams and Nwosu injuries, “but none 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 required him to miss at least the first four games — because they believed he could return by Week 4. Macdonald said Nwosu didn’t have a setback.

“You guys know Uchenna,” he said. “This guy works extremely hard. It was worth a shot, and then having him out doing all the stuff on the field, some of the walk-throughs and things, staying engaged, I think it was the right decision even though it didn’t work out in our favor.”

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

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