Tottenham dropped two precious points against 10-man Southampton on Tuesday as West Ham hammered Watford 4-1 to turn up the heat in the race for a coveted Premier League top-four spot.
Elsewhere on a truncated day of action due to coronavirus postponements, Crystal Palace cruised past bottom side Norwich 3-0 while title-chasing Liverpool prepared to take on Leicester.
Spurs are still unbeaten in the league since Antonio Conte took the helm early last month but failed to make a man advantage count at St Mary's, drawing 1-1.
Adding to their frustrations, Tottenham twice had the ball in the net in the second half but neither goal stood.
Harry Kane's fine strike was ruled out for a narrow offside by VAR and referee Anthony Taylor adjudged goalkeeper Fraser Forster to have been fouled when he dropped the ball under an innocuous-looking challenge from Matt Doherty.
"We have to be disappointed because you have to exploit the situation against 10 men," Conte said, refusing to be drawn on the referee's decisions.
"To play after 44 hours is not easy because you need to recover from the last game," he told the BBC, referring to Sunday's win against Palace.
"Maybe the fatigue caused bad decisions, especially when we arrived in their box. It’s not easy to take a good result in this stadium. In the end we could do better."
Southampton took a deserved lead in the 25th minute with a stunning goal from James Ward-Prowse, who lashed home a first-time effort following a throw-in, leaving Hugo Lloris helpless.
Tottenham had failed to make the most of their limited openings but the game was turned on its head when Mohammed Salisu brought down Son Heung-min in the penalty area shortly before half-time.
Salisu was sent off for a second yellow card and Kane made no mistake from the spot.
Spurs thought they had made their man advantage count when Kane produced a clinical finish from a lofted Harry Winks pass but VAR ruled the goal out and Forster's let-off came midway through the second period.
The home side were on the ropes for most of the rest of the game but Tottenham failed to find a killer touch and left the south coast frustrated.
- West Ham fightback -
West Ham brushed off the disappointment of conceding an early goal at Vicarage Road to strengthen their push for a Champions League place.
The visitors cancelled out Emmanuel Dennis's opener in the 27th minute when Tomas Soucek fired past Daniel Bachmann and two minutes later Said Benrahma put them in front.
Mark Noble increased West Ham's lead from the penalty spot just before the hour mark before Nikola Vlasic completed the rout in stoppage time.
West Ham climb to fifth in the Premier League on 31 points after 19 games, four behind Arsenal and one ahead of Spurs, who have two matches in hand.
"We have had a great year, we really have," said Hammers boss David Moyes. "We have had a lot of wins this year.
"We are back challenging, which was not the situation maybe even two years ago. To be talked about in the top four or Europe this year is a big turnaround."
Palace made the perfect start at home to struggling Norwich, with Odsonne Edouard scoring early before Jean-Philippe Mateta and Jeffrey Schlupp also found the net in the first half.
Liverpool will be desperate to beat Leicester in the late kick-off at the King Power Stadium to close the six-point gap to leaders Manchester City, who have played a game more than their title rivals.
Third-placed Chelsea, in action against Brighton on Wednesday, have confirmed that defender Ben Chilwell needs knee ligament surgery, meaning the England international could miss the rest of the season.