The Gunners went ahead through Alex Iwobi after only three minutes, but the match swung Rennes' way when Benjamin Bourigeaud levelled after Sokratis Papastathopoulos received a second yellow card 41 minutes in.
An own goal from Nacho Monreal put the home side ahead at Roazhon Park, before Ismaila Sarr headed home in the 88th minute to give the Ligue 1 side a solid advantage in the last-16 tie.
And Cech concedes Arsenal will be up against it if they want to turn things around at Emirates Stadium next week.
"The turning point was the red card because they managed to score from the resulting free-kick," Cech began, as per the club's official website. "When we went down to 10 men in the first half, it became a lot more difficult.
"We were unlucky with the second goal because it was an own goal from a deflection, but I thought we were still in the game.
14 & 288 - Petr Čech will make his return to Roazhon Park with Arsenal this evening, 14 years & 288 days after making his last club appearance there as a Rennes player back in May 2004. Return. #RENARS #UEL pic.twitter.com/0qhkm5cF1W— OptaJoe (@OptaJoe) March 7, 2019
"I think the biggest disappointment is the third goal because at 2-1, you go home and you know that there's a result where you've scored away at home, and you can overcome it. We can still overcome a two-goal deficit because, in the end, the goal we scored might play a big part, but we made it a little bit harder for ourselves."
Cech reserved praise for Henrikh Mkhitaryan, who played much of the match at right-back after Shkodran Mustafi was moved into a central position to fill in for Sokratis.
"Henrikh played well there, so credit to him because it's not his natural position but he's done very well for the team," said Cech.
"You need to try to find a way to defend well and I thought we did that really well. They had the advantage because they were fresher as they didn't have any games over the weekend.
"We had to dig deep and with the unlucky second goal, you go and think we'll take 2-1 because maybe there will be an opportunity to score to make it 2-2. Then we lost 3-1, which is a bit of a complication."
The Gunners will now look ahead to a crucial home Premier League clash against Manchester United on Sunday, with both clubs still fighting to secure a top-four finish.