Moffitt's elbow has been causing problems for him recently and forced him to leave practice early Thursday. His left arm was in a sling during Friday's walk-through.
Coach Pete Carroll said Moffitt is likely to undergo surgery to clean up some "loose bodies" in his elbow.
Deuce Lutui will start in place of Moffitt at right guard for the team's preseason opener Saturday against the Tennessee Titans. Rookies J.R. Sweezy and Rishaw Johnson also are expected to see time at the position.
Carroll said the injury is not likely to force Moffitt to miss the season opener against Arizona.