Messi limped off after 21 minutes of the 4-1 win after injuring his left hamstring and he underwent further tests on Monday to determine the extent of the problem.
After receiving the results of those tests, Barcelona said the Argentinian is likely to be absent for between “six and eight weeks”.
A Barca statement read: “According to the club’s medical services, the tests taken on Monday morning by Leo Messi have confirmed that the player has suffered a torn muscle in the femoral biceps of his left leg.
“The approximate time he will be out is between six and eight weeks.
“The first part of his recovery will take place in Barcelona and the second, in Buenos Aires.”
The injury will rule Messi out of both of Argentina’s upcoming friendlies against Ecuador and Bosnia-Herzegovina as well as up to eight matches for Barca.
If he is not available again before the end of the year, Messi would sit out four Primera Division matches, the Champions League clashes against Ajax and Celtic, and both legs of the Copa del Rey last-32 tie against Cartagena.
The good news for Barca is that they boast a three-point lead at the top of La Liga and are already through to the knockout stages in Europe.
The world player of the year, 26, has suffered from hamstring issues in the past, including twice already this season having also damaged the left one in the first leg of the Spanish Super Copa and then the right one at the end of September.
He was out of action for a week the first time and for three weeks the second.
His team-mate Cesc Fabregas, who experienced similar problems while at Arsenal, on Sunday night urged Messi not to try to rush his recovery.
“He needs to take as much time as he needs, to recover and get back to his level. We need him at his best,” he said.
“I had something similar at Arsenal. You think you’re okay, but you’re not.
“I had this injury, I wasn’t right for up to a year and half, it’s a really frustrating injury. You need to take whatever time you need because if you don’t it won’t heal properly,’’ the Spain international told Canal Plus.
Fabregas, who scored two second-half goals in the win over Betis, also picked up a knee injury in the victory and will be sidelined for seven days, Barca announced.
He will be replaced in the Spain squad for the friendlies against Equatorial Guinea and South Africa by his Barca team-mate Marc Bartra.
It is the first time the 22-year-old centre-back has been called up by the reigning world and European champions.