De Luca, 32, has extended his contract with Wasps until the summer, when he will become director of rugby at Uppingham School in Rutland.
After starting his professional career at Edinburgh, De Luca featured for Border Reivers, Edinburgh again and Biarritz before joining Wasps in July.
Wasps are currently top of the Premiership.
Dai Young's side are second in their European Champions Cup pool - one point behind Connacht - ahead of their final pool fixture away to Zebre on Sunday.
"It has been an incredibly difficult decision to retire from the game at the end of the season, but one that was made easier after I met Uppingham School headmaster Richard Maloney and he shared with me his vision for the school," De Luca told the Wasps website.
Young said: "He is a model professional who has done really well each time he has pulled on the Wasps shirt. He has a great attitude and adds a lot to the squad through his international experience."
Former Scotland centre Nick de Luca will retire from professional rugby at the end of the season.