Disappointed Wales coach Gatland believes Rees-Zammit had to follow his heart
Rees-Zammit was to become a central figure for Wales coach Gatland in the next cycle up to the 2027 Rugby World Cup in Australia but instead will pursue a career in the NFL.
"I'm always one of those people who don't dwell on things," Gatland told reporters.
"I don't let it affect me too much. He's made that decision. I want to wish him all the best, like I would with all players and coaches.
"Sometimes they get chances to move on. I've always been supportive of that. If that's been a dream of his, trying to make it in that environment, he'll always regret it if he doesn't take it."
Former England backrow Lawrence Dallaglio says Rees-Zammit's decision is a sign of the times in rugby.
"Some may see this as a strange choice but it says a lot about the pathways in rugby that players are looking elsewhere," Dallaglio said on the social media platform X.
"At 22, good luck to him. Take a sabbatical and if it doesn't work out, come back. If I was playing now, I would consider 12 months in Japan post-Rugby World Cup to freshen up."
With Leigh Halfpenny having retired and Liam Williams in Japan, making him ineligible for selection, Rees-Zammit would have been an option for Wales at fullback.
"Cai Evans can play fullback. We see him as one to develop," Gatland said. "Tom Rogers can play there. Long term, I think that's his position. He's probably not quick enough internationally as a winger, although he's done a good job.
"Ioan Lloyd can play there (fullback). We've got lots of options. Cam, at the moment, may not be available for the first couple of games as he has a jaw injury."
Gatland named lock Dafydd Jenkins (21), as Wales' second youngest captain after Gareth Edwards (20), a bold move after hooker Dewi Lake and back row Jac Morgan shared the duties at the World Cup. Both are currently injured.
"He's (Jenkins) the type of guy who gets on with his job. He's one of the last out of the gym. He works hard on his preparation and on the laptop looking at the opposition. He'll lead by example," Gatland said.
Number eight Taulupe Faletau is unlikely to feature in the Six Nations having not played since breaking his arm at the World Cup. He now has a calf problem.
"It will probably keep him out for the Six Nations," Gatland confirmed.