The Panthers will face the defending Super Bowl champions Saturday at 8:15 p.m. ET.
"Star will not play this week," coach Ron Rivera said in a conference call with Seattle reporters. "He broke a small bone in his foot, and he had surgery this morning to repair it. It's one of those things that hopefully we get the opportunity to move on [in the playoffs], and if we do, he'll get to play."
Lotulelei will be out at least two weeks.
Lotulelei missed two games earlier this season. The Panthers went 0-2 without him but held up well against the run, surrendering just 89 rush yards per game and 3.49 yards per carry, according to ESPN Stats & Information.
"Colin Cole will assume a bigger role for us," Rivera said. "He's been a solid and steady force for us, such a space-eater inside, holds the double-team at the point of attack and helps to allow our linebackers to run."
Cole called Lotulelei a "force in the middle" for us.
"We have a very good rotation going, and he'll be sorely missed," he said. "A great athlete. A great competitor. But that's the nature of the business.
"We're not counting him out. If we keep this thing going, he'll be able to come back to us if we're still playing in February."
Defensive tackle Kawann Short said Lotulelei was in the training room when the team returned from practice Tuesday.
Lotulelei started all but three games this season. He injured an ankle during a Week 10 game at Philadelphia and missed his next two starts. He was playing his best of the season down the stretch, collecting seven tackles and two sacks in the regular-season finale against Atlanta.
"Star has really come on the last few weeks for us and has been playing real well," Panthers linebacker Luke Kuechly said. "It's unfortunate that he won't be playing. ... It's kind of been the theme to our season. One dude can't play and the next dude has to jump up and play."
Wide receiver Philly Brown also did not practice for the second straight day Wednesday after injuring his shoulder in Saturday's 27-16 playoff win over the Arizona Cardinals. He is listed as day-to-day.
ESPN.com Seahawks reporter Terry Blount contributed to this report.