The Greek defender was shown a second yellow card shortly before half-time by referee Ivan Kruzliak for pulling back Ismaila Sarr as the winger bore down on goal.
Papastathopoulos was booked just eight minutes earlier for a challenge on Hatem Ben Arfa on the edge of the box.
With Rennes growing into the game, the centre-back had no excuses as he tripped up Sarr and was directed towards the tunnel by Kruzliak.
To make matters worse for the Gunners, Rennes scored from the resultant free-kick.
Benjamin Bourigeaud struck a sweet half-volley from 25 yards out which flew past Petr Cech after his initial effort had hit the wall.
Arsenal fans instantly fumed at the red card, believing it was Sarr who fouled Sokratis.
“Sarr elbows Sokratis in the face – Sokratis sent off,” one wrote.
“Second yellow for getting fouled [thinking face] aiight ref,” another opined.
More supporters flooded in with choice words for the ref, such as: “Obvious dive”.
“This ref needs to get sacked asap!” said another, alongside: “HE HIT PAPA IN THE FACE! This reffing is ridiculous”.
Although the fanbase had sympathy with Papastathopoulos, his manager did not.
The 30-year-old embarrassedly exited down the tunnel and looked at his manager, who was on just along the touchline.
But the Spanish coach refused to look at this dismissed centre-back, turning his back away from him.
Already without first-choice defenders Rob Holding and Hector Bellerin, Papastathopoulos’ red has sparked more trouble for the second leg at the Emirates.
Following the red card, Mustafi was moved from right-back to his preferred central role in defence, while playmaker Henrikh Mkhitaryan was bizarrely switched to right-back.
Arsenal went on to lose the game 3-1, with Nacho Monreal diverting the ball into his own net in the 65th minute, before Sarr headed home in stoppage time.
The shambolic nature of Monreal’s unfortunate own goal was exacerbated by Pierre-Emerick Aubameyang, who turned away from his defensive duties moments before the goal was scored.