The Iranian champions dominated the first-half and should have scored several goals, before going a man down and eventually hanging on as the Qataris came close at the death
Sepahan dominated the chances in the first-half but midfielder Emad Obrahimi scored the only goal of the game on 13 minutes.
The game turned on its head when teenager Akbar Imanighareh was sent off on 58 minutes and Al Sadd came close to levelling the contest in stoppage-time when his free-kick hit the woodwork.
Early on it was all Sepahan, buoyed by the inclusion of key Brazilian midfielder Fabio Januario, who had been expected to miss the game after an old injury resurfaced earlier this week.
Imanighareh then tested Al Sadd keeper Mohammed Saqr from range, forcing a corner which resulted in the goal.
Januario's deep cross was only partially cleared by Saqr, before Obrahimi pounced on the loose ball, unleashing a long-range shot which travelled through a packed box and caught the Al Sadd keeper off guard.
The pressure continued with Januario peppering Saqr's goal with two left-foot efforts, while Al Sadd struggled for opportunities with Nadir Belhadj booked for diving inside the box as he attempting to create something for the Qataris.
Emad Mohammed and Beikzadeh blazed efforts off target before the interval, but Sepahan appeared to go into their shell in the second-half as they attempted to protect their lead.
The situation for the hosts got even more precarious when Imanighareh bundled over new Al Sadd signing Mamadou Niang on the halfway line, prompting referee Ben Williams to give him his marching orders for his second bookable offence.
Al Sadd attempted to make the most of their advantage, although the second-half failed to offer many clear-cut opportunities as Sepahan sat back.
Sepahan keeper Rahman Ashadi did well to deny Niang on the left-side of the box on 77 minutes, while a frustrated Abdulkader Keita fired high and wide on 89 minutes.
However, Al Sadd would have one final chance when a stoppage-time free-kick cannoned into the woodwork and away from goal with Ashadi beaten.