The former world No.1, a six-time champion in Florida, was bundled out the competition at the second round stage by a determined and focused Benoit Paire.
The temperamental Frenchman was a 6-3 6-4 winner over Djokovic, and he will encounter another Serbian, Filip Krajinovic, in the last 32 later this week.
Djokovic, who has won the sunshine double on four occasions, has not registered a single victory since the Australian Open. It was another listless display from the 30-year-old, and his latest comeback is yet to gather pace.
Prior to the start of the tournament the Serbian stated he was finally pain-free after a difficult and challenging 12 months, however he looked far from fully-fit in the heat of battle.
Djokovic appeared to be limping at times in the opening set – and his downbeat and subdued demeanour did not suggest he was at the peak of physical fitness.
The inexplicable misses that defined his performance in his loss to Taro Daniel in Indian Wells resurfaced in his latest setback. He rallied in the second set after a first set collapse, but it was yet another below-par performance.
Paire has a tendency to implode while holding a promising advantage against higher ranked opponents, but he rarely wavered from his task. His serve and backhand proved to be a formidable combination, and he was rarely troubled.
The first six games went with serve before the Frenchman made his move. Djokovic blasted a routine forehand into the middle of the net – losing his balance in the process – to drop serve and fall 4-3 behind.
The Serbian never appeared likely to hit back – and eventually he lost serve again. From a 40-0 position, he conspired to lose the ninth game and the opening set.
Despite his woes, there was no emotional outburst from Djokovic. There was barely a flicker of annoyance, and he maintained a calm exterior despite falling 4-2 behind in a must-win second set.
Spurred on by the crowd, the 12-time major champion put together a string of quality shots to retrieve the break and rekindle his hopes. It was a productive passage of play for Djokovic, however he faltered when serving to stay in the match.
It was a morale-boosting win for Paire, but another confidence-sapping loss for his beleaguered opponent.