Henderson suffered a heel injury during the Reds' win over Manchester City on New Year's Eve and has sat out the last two games - against Sunderland and Plymouth.
Coutinho, who has been sidelined for seven weeks, is ready to return after recovering from an ankle ligament injury and the Brazilian could play a part at St Mary's.
The Reds, who are currently on a seven-game unbeaten run, are expected to make several changes from the young side that drew with Plymouth in the FA Cup on Sunday and Adam Lallana may get a start against his former club.
Jurgen Klopp's men won 6-1 at St Mary's in last season's League Cup quarter-finals while the Premier League meeting on the south coast earlier this season finished 0-0.
Liverpool last week