The game was only nine minutes old when Messi was caught on TV cameras fiddling with his left sock.
He then appears to take something out of it before putting the pill in his mouth and resuming the game.
According to Radio Catalunya, the tablet was a glucose pill that he uses to control the nausea he occasionally suffers before and after matches.
Whatever it was seemed to work as Messi netted his 100th goal in UEFA competitions to help Barcelona to a 3-1 win.
Barca boss Ernesto Valverde was quizzed on the incident after the game, where he made light of the matter.
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“I don’t know if he took a glucose tablet,” said Valverde.
“If it made him score a goal, then he should take a load of them… But I do know the players do take glucose.”
Valverde then joked he hoped to see Lionel Messi score 200 goals after his second-half free kick at the Nou Camp last night.
“I hope he reaches 200 goals this season!” he said.
“His numbers validate what we see every day, he’s beating statistics that seemed impossible. He’s been doing it for a long time now, constantly breaking down barriers.”
Messi’s strike helped extend Barcelona’s unbeaten run to 11 games, which includes 10 wins.
Valverde has only been in charge 100 days but the run of form has won over sceptical supporters.
“I don’t know if the fans are enamoured with me just yet,” he said. “It’s true the results are good. We are top of La Liga, top of our Champions League group… But tomorrow’s another day, Saturday’s another game. The dynamic can change, football’s fanciful like that.
“In August, after the Super Cup [defeat to Real Madrid], we were no good, now we are… So we are going to cross our fingers and keep working hard.
“We are happy today because it’s not easy to win in the Champions League. There are no easy games, as we are seeing with other teams.
“Olympiakos came to defend close to their area and to surprise us on the counter-attack. We then had the set back of the red card and we couldn’t keep so high up the pitch. When that happens, the rhythm changes.
“But we are satisfied because we were able to open up the game in the second half despite having a man less.”