NSRI were contacted around noon following reports from police of two people in difficulty in the surf at Souwesia beach, near the Great Brak River, said spokesman Craig Lambinon.
Police, paramedics and Mossel Bay fire and rescue services also responded.
When paramedics arrived on the scene, they found a 23-year-old man, who was from George, on the beach.
CPR (cardio pulmonary resuscitation) was performed, however the man was declared dead shortly afterwards.
An extensive sea and shoreline search took place for the second man, who was also 23-years-old and from Geroge.
No sign of the man was found, with the police dive unit having taken over the search for the man.
It was believed the two men were swimming and may have been caught in rip currents, said Lambinon.
Police have opened an inquest docket.
The body of the man found on the beach was handed over to forensic pathology services.
The NSRI urged caution on the coast while the New Moon Spring Tide, which peaked this weekend, continued into the latter part of the week as it brought exaggerated high tides, low tides, and stronger than normal rip currents.