Shane Long picked up a suspected hamstring injury after ending an 18-game goal drought with the Republic of Ireland on Sunday.
The Saints striker opened the scoring in a vital 3-1 World Cup qualifying victory in Moldova for Martin O'Neill's men.
Long, who had gone into the game having failed to score in his previous ten league and cup games for Southampton and in his last eight appearances for his country, finished off a slick move in the second minute.
The 29-year-old's last goal for Saints came in the 4-2 home win over Manchester City on May 1.
But the former Hull City and West Brom star could not finish the match, hobbling off just past the hour mark.
James McClean sealed the Republic's triumph with two goals in the space of seven second-half minutes after Moldova had cancelled out Long's effort in Chisinau.