Southampton had to play 80 minutes without Danish defender Jannik Vestergaard after he was sent off for a foul on Jamie Vardy.
But James Ward-Prowse’s second half penalty briefly put Ralph Hasenhuttl’s side ahead before Jonny Evans headed Leicester’s equaliser.
Leicester remain in third place, but fourth placed Chelsea would close the gap to just two points if they beat struggling Fulham on Saturday.
Fourth place will be reduced to a Europa League qualification spot if Chelsea win the Champions League, Arsenal win the Europa League and both clubs finish outside the top four.
So Leicester need to hang onto third place to be sure of qualifying for next season’s Champions League.
Fourth place might still be enough for Brendan Rodgers’ team, but they have only four matches left to guarantee their berth in Europe’s elite club competition.
In an FA Cup semi-final rematch after Leicester’s 1-0 win at Wembley two weeks ago, Southampton gave a better account of themselves to end their three-game losing streak.
Leicester had powered to a top-flight away record 9-0 win against Southampton on their previous visit to St Mary’s in 2019.
But they found it much tougher this time and should have been behind early on when Nathan Tella, unmarked eight yards from goal, shot weakly at Leicester keeper Kasper Schmeichel.
Southampton were reduced to 10 men in the 10th minute after Vestergaard’s slip left Vardy clean through on the edge of the penalty area.
Vestergaard responded to his blunder with a desperate lunging tackle, but although the centre-back made contact with the ball, he clattered into Vardy’s ankle in the process, earning a red card from referee Robert Jones.
Despite their numerical advantage, Leicester struggled to take control and Southampton winger Nathan Redmond threatened with a long-range blast that Schmeichel palmed away.
It took over half an hour for Leicester to carve out a serious chance when Kelechi Iheanacho picked out Youri Tielemans and the Belgian’s low drive forced a fine save from Saints keeper Alex McCarthy at his near post.
Southampton were battling impressively and they took the lead in the 61st minute thanks to a helping hand from Iheanacho.
Stuart Armstrong’s shot thumped into Iheanacho’s out-stretched arm and Jones pointed to the spot, with Ward-Prowse smashing the penalty past Schmeichel for his ninth goal this season.
James Maddison’s long-range curler was tipped over by McCarthy, who made an equally good stop from Ayoze Perez’s rising strike moments later.
Finally hitting their stride, Leicester equalised in the 68th minute as Evans met Iheanacho’s pin-point cross with a powerful header that gave McCarthy no chance.
Vardy, set up by Maddison’s pass, could have won it for Leicester with seven minutes left, but McCarthy made a brilliant save with his legs to repel the close-range effort.
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