The 29-year-old England striker crashed into the advertising boards during the 3-0 win over Hull City at Old Trafford last Saturday and was subsequently omitted from the 2-1 victory over Stoke in midweek.
A subsequent scan revealed no significant damage and Rooney is set to return to the match-day squad alongside Northern Ireland defender Jonny Evans, who has finally shaken off the ankle injury that has plagued his season.
Less pleasing news for Van Gaal is the continuing absence of summer signings Angel di Maria, who has a hamstring injury sustained during that victory over Hull and Daley Blind, who is still around a month away from returning a knee problem.
United will be looking for a fifth straight victory when they travel to St Mary’s and can wrest third spot from Saints, who have lost their last two games to Manchester City and Arsenal.
Watch Southampton v Manchester United live on Sky Sports 1 at 8pm on Monday.