Grimes, who was set to make his 120th start Sunday, suffered a groin injury during Friday's practice and did not travel with the team, leaving a young and inexperienced secondary vulnerable against Drew Brees and one of the league's top offenses.
The Bucs' No. 2 cornerback, former first-round draft pick Vernon Hargreaves, struggled last season and had to fight off rookie Carlton Davis during training camp to keep his job. Hargreaves was able to keep his job as a starter, but he'll be battle-tested right out the gate, covering Pro Bowler Michael Thomas.
"Some things you've just gotta go through and deal with and move on and learn from. That's kind of the stage I'm in: learning from the past, moving on and hopefully correcting it and being better," Hargreaves said.
As far as Thomas, "I don't know if there is a key to stopping him, but you've just gotta know where he's at on the field," Hargreaves said. "You've gotta be aggressive with him. You've gotta be physical with him."
Grimes' absence creates a lot of potential shuffling of the Bucs' defensive backfield because Hargreaves moves inside during nickel situations.
The Bucs could leave him outside the whole game, having Davis start opposite him, or go with third-year corner Ryan Smith, who started 10 games last season but at times was a liability.
At nickel, they could have rookie M.J. Stewart, who returned to practice this week from a foot injury, or Javien Elliott, who was called up from the practice squad after DeVante Harris was placed on injured reserve.
"I think it was a good situation when we had to line up and play [Evans] for three or four days at the nickel position," defensive coordinator Mike Smith said. "It gives us flexibility. It also gives him a much better understanding of what the other guys are doing around him on the defense. He's a safety that's got athleticism of a corner."
In two games against the Saints last season, the Bucs' defense surrendered 407 and 323 yards of offense. In those games, Brees had passer ratings of 131.9 and 108.3, with completion percentages of 81.5 percent and 73.3 percent.
When Grimes did play the Saints last year in Week 17, he gave up just one completion for nine yards, according to Pro Football Focus.