WARNING: Spoilers for Avengers Infinity War ahead.
The character, played by Josh Brolin, wiped out half of humanity at the end of the record-breaking Marvel hit.
Among the fatalities were a great number of Marvel favourites, including Peter Parker, Doctor Strange, Wanda Maximoff, King T’Challa and Bucky Barnes; as well as most of the Guardians of the Galaxy.
Speaking in a video on Twitter, Lee quipped: “Holy smoke… I go out of town for a few days and when I get back I find out that Thanos has destroyed everything – all my characters!
“That’s the last time I take a discount vacation!”
He added: “Well, unfortunately it means a lot of new work for me.
“Don’t worry, before you know it I’ll have our friends up and at ‘em, and if I were Thanos I’d start getting out of town!”
The clip has racked up 2.7 million plays on Twitter at time of writing, with the help of 70,000 retweets.
“Hard not to love you good sir! Thanks as always,” wrote one fan.
Referencing Parker’s final moments, another quipped: “Thanos – ‘I don’t feel so well Stan…’”
Infinity War will be followed by the as-yet-untitled Avengers 4 next year, with several of the deceased characters expected to appear in some capacity.