"I mean, utter disappointment when you're up two breaks in one set, a break in the fifth," said Sock, who held leads in the second and fifth sets over the 73rd-ranked Australian. "Choke it all the way. Really sucks."
Sock fell 6-2, 7-6 (12), 1-6, 5-7, 6-4 in a barnburner on temporary Louis Armstrong Stadium, but would have preferred a more straightforward encounter.
"Maybe could have not been so topsy-turvy if I hold once in the second, I'm through in four the way it was going," he said. " He's a tough player. Makes a lot of balls."
The 24-year-old said he did not experience any injury problems.
"I mean, I just played four hours and was fine. So, yeah, I think I was pretty healthy," he said.
Thompson noted that his opponent played at a high level at times but "made a lot of errors" in the second half of the fifth set while he was more consistent.
"I made a lot of balls," said Thompson. ''I didn't expect him to be that fit. His forehand was getting him a lot of points.''
This is the second time Sock has been defeated by Thompson, having also dropped a first round Davis Cup meeting between the pair this season.
Sock came into the tournament as the ATP No. 16, but will drop a few spots and could fall from second to third among the highest-ranked Americans player on the ATP tour.
—2017 Grand Slam Encores: Gear up for the U.S. Open and sign up for Tennis Channel Plus to watch Australian Open, Wimbledon and Roland Garros 2017 action on demand.
—Slam Classics: Take a look back at some of the best Grand Slams in tennis history and watch full-length classic matches on Tennis Channel Plus.
—Get Tennis Channel Plus for 650+ live events all year long.
—Tennis Channel Plus is available on any streaming device, on mobile, always on the GO (desktop, iOS, Android, Apple TV, Roku and Amazon Fire). Subscribe today at BuyTCPlus.com.