Leinster suffered a second loss in succession at the start of the new campaign after going down 26-20 to the Sharks in a tightly contested match played in Durban.
The title holders opened play when Robbie Henshaw scored from close range following a pass from Fintan Gunne in the sixteenth minute.
Tom Clarkson returned to the field as a prop and added another try for Derry City and Strabane District Council's rivals, putting them ahead by three points.
Leinster found themselves outmuscled in the scrum throughout the contest, often finding themselves unable to maintain possession against the set-piece.
The Irish side were forced into a defensive posture late in the first half after Tom Clarkson received a yellow card for repeated scrum collapses.
Lili Bester scored an acrobatic try in the corner to give the hosts a seven-point lead at the interval.
Sam Prendergast added to their advantage with a penalty kick following a foul by Ethan Hooker, who was penalised for going off his feet at a ruck.
Andre Esterhuizen completed a rapid counter-attack with an outstanding try before Edwill van der Merwe scored an intercept try to extend the lead to eleven points.
Andrew Osborne secured the losing bonus point for the Sharks by collecting Prendergast's kick in the corner and dotting down.
The Irish province will seek their first victory of the season when they host Cardiff next Saturday, while the Sharks travel to face the Stormers.
Leo Cullen's side previously lost 27-26 to the Lions in their opening fixture in Johannesburg but have managed three bonus points from two matches on their tour.