Ranked 32nd in the world, Pospisil was due to play Frenchman Gael Monfils, but he withdrew with a wrist injury. Pospisil had the momentum going into the match against No. 52 Andujar, who got into the draw as a lucky loser, after making the semifinals last weekend in Basel.
But he said his head wasn't in the game Tuesday.
"I had no physical issues," Pospisil said. "I was just burned out mentally. I was not ready to fight, I'm very disappointed right now. It's true I've had a great season but it's disappointing to lose like that."
Pospisil went down with 62 unforced errors, 38 off of his usually reliable forehand. His lack of fire was evident in the opening game when he dropped serve in the 37-minute first set, despite dominating Andujar with 12 winners.
Pospisil rallied in the second set to take it with a pair of breaks but failed to keep up his intensity in the third set as the rigours of the demanding season began to take a toll.
Andujar earned a 4-2 lead on a break but was then unable to easily serve out the win. Instead, the Spaniard lost serve leading 5-2 and missed a match point chance a game later as Pospisil hammered over an ace.
Pospisil saved three more match points a game later before Andujar managed a passing winner to end the struggle.
The 23-year-old Pospisil said that several months of travelling in Asia and Europe since the U.S. Open finally hit him.
"I've been on the road for eight or nine weeks, and I've been struggling the last few weeks, even if I did well last week," he said. "It was definitely tough to play today. I didn't play well at all, credit to him, he played solid, but I'm not happy with my game."
Pospisil said he's anxious to move on.
"I'm bitter now, but I've had a great year for sure," he said. "I'll try to forget this match as quickly as possible and look back on a positive year."
His 32nd ranking is a career high for Pospisil, who now has a chance to be seeded at the Australian Open in January. He started 2013 ranked 128th.
Pospisil said he will take a few weeks off before beginning his pre-season training in Florida.
Tenth-seeded Milos Raonic of Thornhill, Ont., opens play Wednesday against Robin Haase of the Netherlands. The Canadian star is vying for spot in the World Tour Finals in London next week.
In other play Tuesday, Kei Nishikori of Japan put an end to Jo-Wilfried Tsonga's bid for a World Tour Finals spot by defeating the Frenchman 1-6, 7-6 (4), 7-6 (7) in the second round while ninth-seeded Richard Gasquet outlasted Fernando Verdasco 7-5, 6-7 (6), 6-3 in another second-round match to stay in contention for the tournament in London.
Rafael Nadal, Novak Djokovic, David Ferrer, Juan Martin del Potro and Tomas Berdych have already qualified for the tournament in London next week. There are still three spots up for grabs as Andy Murray withdrew from the season-ending event to recover from back surgery.
In first-round matches, Grigor Dimitrov of Bulgaria rallied past two-time semifinalist Michael Llodra of France 6-7 (5), 6-3, 6-3.
Kevin Anderson of South Africa, Marcel Granollers of Spain, Ivan Dodig of Croatia, French wild card Nicolas Mahut and Polish qualifier Michal Przysiezny also moved into the second round.
— With files from The Associated PressSuggest a correction