Rickie Lambert ensured Southampton remain favourites for automatic promotion from League One after inspiring the victory over Hartlepool.
Visiting keeper Scott Flinders saved well from Lambert, Adam Lallana and Guly Do Prado in the first half.
Pools had captain Sam Collins sent off after he fouled Lambert in the box, leaving the striker to pick himself up and score the resulting penalty.
The Saints rounded off the win when Jose Fonte nodded in Lambert's cross.
Southampton remain second in the table, level on points with third-placed Huddersfield but with a vastly superior goal difference and a game in hand.
Hartlepool drop one place to 15th.
Southampton manager Nigel Adkins told BBC Radio Solent:
"Credit to Hartlepool, they've been well organised. We had to be patient to break them down but we got there in the end.
"The players were endeavouring to win a game of football out there and they've done that.
"We'll be in again Tuesday from a recovery point of view, just to get the bodies ready for another massive weekend."
Hartlepool United first-team coach Mick Wadsworth told BBC Tees:
"Once we went to 10 men it made it very difficult. Referees' decisions change games, the penalty, my centre-half says he didn't touch him.
"He's very angry. That means a red card, three-match ban, and I'm very angry about that, we'll have to look at the DVD.
"Directly before their second goal there's a blatant foul on Michael Mackay, 10 yards in front of where we give a foul away from which they score, it drives you mad, the whole balance of decisions."