Nadal, who has said he expects to retire after the 2024 season, returned to the tour in Brisbane in January after nearly a year out with a hip flexor injury and the Spaniard has not played an ATP tournament since due to a muscle issue.
The 22-time Grand Slam champion looked set to make another comeback at the Monte Carlo Masters this month but withdrew days before the start of the claycourt tournament, saying his body would not allow him to play.
Nadal has won the Barcelona title 12 times and is drawn to play Flavio Cobolli on Tuesday, and while there has been no word on his status Tsitsipas said the Spaniard would have no trouble finding form on his favourite surface.
"I wouldn't be surprised if we saw Rafa in the final of Barcelona, because that's something he has done over and over again for years and years," Tsitsipas, who won the Monte Carlo title for a third time on Sunday, told reporters.
"What he does have is this competitiveness and this fierce tennis when he gets into the momentum that sometimes feels like on the outside perspective unstoppable ... I think he's the ultimate challenge on clay.
"Whether he's playing now at, let's say, later stages of his career or the ones before, what he has now that he didn't before is experience, and he for sure knows ways to win points and to prevail more in economy mode than before."
World number seven Tsitsipas, a three-time runner-up in Barcelona, will aim to carry his good form from Monaco to Spain after winning his first title of the season with a 6-1, 6-4 victory over Casper Ruud.
"I did need a week like this a lot, especially (after) the rough months I've been through the latter half of 2023 until now," Tsitsipas said.
"It hasn't been the best of times in terms of where I wanted to be, so getting back here and winning the title is something I was definitely not aiming for and it came naturally."
