We employed catch data from 2 fishery-independent shark surveys conducted from 2009–2012, as well as stable isotope analysis, to investigate potential effects of the 2010 Deepwater Horizon oil spill on large coastal fishes in Florida's Big Bend region. The catch-per-unit-effort of 5 indicator species (3 sharks and 2 teleosts) varied significantly among years in only 2 cases. The stable isotope profiles were significantly different among years in 2 of 5 indicator species, but the relative differences were small, and patterns were not consistent among taxa analyzed. Our results provide no evidence that the Deepwater Horizon oil spill had a significant effect on the relative abundances and food-web structure among large coastal fishes in Florida's Big Bend.