Ireland legend Sexton, the 2018 World Rugby Player of the Year, was one of the surprise exclusions from Gatland's 37-man selection for the upcoming tour of South Africa.
Sexton misses out despite the fly-half playing a key role on the 2017 trip to New Zealand, with Gatland expressing some concerns over the 35-year-old's "durability" and instead calling up Dan Biggar, Owen Farrell and Finn Russell.
"There's no doubt that that was one of the toughest decisions that we had to make," said Gatland at a news conference on Thursday.
"I've got a huge amount of respect for Johnny and his quality, but it's such a pivotal position for us and it's about sending a message to the 10s that we have selected that we have the confidence and belief in them to do a job.
"When we looked at where we were going in South Africa probably the thing that kept coming back to us was Johnny's durability, being able to put a string of matches together consecutively, and big matches.
"He has been rested on a number of occasions and unfortunately that's possibly what swayed it for us in terms of us not having the confidence that he can get through what's going to be a tough, physical tour."
Billy Vunipola was also a notable absentee from the list, while other big calls saw Wales centre Jonathan Davies, England prop Kyle Sinckler and Ireland second row James Ryan left out.
However, Gatland did find room for Exeter Chiefs number eight Sam Simmonds, who has not played a Test for England since March 2018.
The Lions will face the Springboks in Tests on July 24, July 31 and August 7.