Villarreal were narrowly defeated 2-1 away by Real Betis, leaving them 18th in La Liga with just seven matches remaining.
However, the visitors had a chance to grab an equaliser in the 89th minute from the penalty spot, with Cazorla the man to step up
But the former Arsenal man – the boyhood Villarreal star disappointingly saw his spot-kick saved, hitting his penalty straight down the throat of Betis goalkeeper Pau Lopez.
A draw would have taken Villarreal up to 17th place, one point above relegation rivals Valladolid. But instead, they slipped back into the relegation zone at a crunch point in what has been a very tough season.
And following the match, Cazorla was heartbreakingly left in floods of tears inside the stadium as one of Villarreal’s management staff tried to console the playmaker.
The 34-year-old, who has made a remarkable comeback from an achilles injury after 668 days out which nearly saw him lose his leg, will be determined to reverse his fortunes when The Yellow Submarine step onto the pitch next.
Villarreal take on Valencia in the Europa League quarter-finals on Thursday, with the winner over the two legs set to face either Arsenal – Cazorla’s former club – or Napoli in the last-four.
After that, Villarreal face Girona away with three points a necessity against a team not out of the relegation battle just yet.