The Springbok hooker missed the 35-29 loss to the Cheetahs due to injury, but returns as one of four changes made by director of rugby Gary Gold.
The Lions were also beaten last weekend, going down 22-8 at the hands of the Hurricanes.
Du Plessis said both South African franchises should not have lost on the opening weekend, and he expects another feisty derby on the east coast.
“If you look at stats, we should have won last week, so too the Lions,” said Du Plessis.
“I don’t think you should look at stats to determine how efficient you are.
“Our execution and intensity wasn’t up to standard on the weekend, but we still back our system 100 percent. We look forward to the challenge that’s going to come our way on Saturday.”
Du Plessis sat out last week due to a shoulder problem, but returns to replace Kyle Cooper in the starting XV.
“I’m feeling good at the moment,” the skipper said.
“I felt disappointment when I was sitting in the stands watching last week.
“We are a much better side than the way we played, and we let ourselves down in a lot of areas on the field. We have to improve this week.”
The Sharks have also handed a debut to Lubabalo Mtyanda, at lock, following an injury to English import Mouritz Botha.
There are also starts for Odwa Ndungane at wing and Dale Chadwick in the front row, at the expense of the injured S’bura Sithole and Tendai Mtawarira respectively.
The Lions, meanwhile, made two changes to their team. Jacques van Rooyen comes in at prop for Schalk van der Merwe, and Warwick Tecklenburg for injured flank Jaco Kriel.
Uncapped pair JP du Preez, who is just 20, Ruaan Lerm and Harold Vorster are on the bench at a venue where the Lions have never won at Super Rugby level.
“We are looking forward to the trip down to the coast as we enjoy the local derbies and believe this to be a crucial encounter for both sides,” Lions coach Johan Ackermann said.
“Both teams have a lot to play for as we both went down in our first games of the season – both at home – last weekend.
“The Sharks will no doubt come out firing, but we will just follow our processes and look to capitalise where we did not last week. We will really need to use our opportunities and limit our mistakes.”