Refuge waters include Tarpon Bay and mangrove estuary on the north side of Sanibel and the Sanibel River at the Bailey Tract. The estuary provides excellent boat fishing year-round. Wildlife Drive provides good shore fishing and crabbing opportunities year-round. The Bailey Tract provides freshwater fishing opportunities year-round. Small boats, kayaks and canoes can be launched from Tarpon Bay Recreation Area. Cartop-size boats, kayaks and canoes may be launched from the right-hand side of Wildlife Drive into the estuary, but vessels must pole, paddle or float in the area of Wildlife Drive. There is Gulf of Mexico access via the Pine Island Sound. Available freshwater species include largemouth bass, bluegill and gar. Saltwater species are bluefish, spotted seatrout, flounder, red drum, spot, pompano, Spanish mackerel, snook, tarpon, bonefish, mangrove snapper and mullet.
Salt water fishing is popular along Wildlife Drive, in Tarpon Bay, and in the backwaters of the Refuge. Common fish include sheepshead, snook, redfish, and spotted sea trout. All Florida state fishing laws apply.