Interviewed on Mike & Mike In The Morning on ESPN Radio, Tressel said the Buckeyes' staff has to be cautious in determining whether Wells can play at all against the Trojans with a foot injury.
"Right now, I would call him doubtful, but we'll see how he wakes up [Friday] morning and what's ahead," Tressel said. "I think we have to be smart medically. Beanie has to be smart and be honest about how he feels. We have to be smart as coaches.
"Like anything else, one play can hurt you as much as 23 plays. I would think we would be able to use him sparingly or not at all."
On Thursday night, the news for Buckeyes fans appeared more hopeful, as ESPN college football analyst Brent Musburger reported that Wells would be a game-time decision.
An Ohio State spokesperson told Musburger that after Wells iced his foot on a Thursday morning flight from Columbus to Los Angeles, Ohio State officials were "a little more optimistic." When Tressel said Wells was doubtful earlier, he meant Wells probably wouldn't play if the game were Thursday night, according to the spokesperson.
Tressel said there was lingering soreness for Wells in his right foot after he worked out Wednesday night. Wells did not practice with the team Thursday morning just before it departed for Los Angeles.
Wells injured his right foot in the fifth-ranked Buckeyes' opener against Youngstown State. He did not play last week against Ohio University and has not had contact in partial practices this week.
On Tuesday, Tressel said Wells would play against USC, and how much would depend on his progress in practice. On Thursday, Tressel did not rule out the possibility of the junior seeing action, but he did not sound optimistic.
"Beanie practiced about 20 carries yesterday, and maybe 20 percent of the practice," Tressel said. "We didn't have him work today. He had more soreness this morning than we had hoped for. A late afternoon practice followed by a morning practice, we're hoping that's a little bit of the reason why. So we'll just have to play it by ear."
Co-offensive coordinator Jim Bollman said after Wednesday night's practice that Wells was about 75 percent healthy.
"The chances of him being 100 percent are not high, I would think," Bollman said. "That would be a miraculous recovery."
Ohio State is a 10½-point underdog against the Trojans in the first meeting between the teams in 18 years. USC has won its past seven meetings against Big Ten teams by an average margin of 27.8 points.
"The interesting thing about college football at our level is that the playoffs begin in September," Tressel said Friday. "Every game is a big one.
Keep in mind that it is September. I think just the excitement of playing two programs that have had their share of success what a great opportunity."
With Wells out of last week's come-from-behind 26-14 victory over 33½-point underdog Ohio, redshirt freshman Dan Herron, sophomore Brandon Saine and senior Maurice Wells handled the load at tailback. They have also been seeing most of the action in practice this week, with Wells working out Monday and Tuesday on his own under the supervision of team trainers.
Tressel said Thursday the three backups would share the job of replacing Wells, who rushed for 1,609 yards and 15 touchdowns last season and was considered a top Heisman Trophy prospect this season.
"I would call it more by committee," he said. "Now if someone starts really feeling it, no matter who that is, you would [play them]. But we're pleased with all those guys."
Tressel said team doctors, trainers and the coaching staff would monitor Wells' condition and then consult with him before ruling on whether he will play in the game at the Coliseum.
He said the Buckeyes' playbook would not be severely hampered by Wells' absence. But he did say that it still might come as a shock to Wells' teammates if he cannot play in a game of this magnitude.
"Our guys have seen that we've practiced for quite some time without him," Tressel said. "I suppose maybe when you get to the realization that, OK, maybe he won't play, then perhaps there's a 'Man!' type of thing. But we've got to go [on]."
Last season, Wells posted per-game averages of nearly 124 yards and 21 carries. Without him last week against Ohio, Herron (12 carries, 50 yards), Maurice Wells (9 for 48) and Saine (5 for 15) combined for 113 yards on 26 carries against the Bobcats, who led 14-6 midway through the third quarter and 14-12 heading into the fourth.
Information from The Associated Press was used in this report.