Our objective was to examine the effects of high hydrostatic pressure (HHP) on physico-chemical properties and bacteriological quality of caiman (Caiman crocodilus yacare) meat. Caiman tail meat was cut into 25 g chunks, individually vacuum packaged, and allocated to four treatments: non-treated (NT; not subjected to HHP), and samples subjected to HHP at 200 MPa (P2), 300 MPa (P3), and 400 MPa (P4). Physico-chemical properties, fatty acid profile, and bacteriological quality were evaluated. All HHP treatments (P2, P3, and P4) demonstrated lower (P < 0.05) microbial loads than NT. HHP decreased (P < 0.05) n-3 polyunsaturated fatty acid content and hypocholesterolemic/hypercholesterolemic ratio. However, HHP increased (P < 0.05) n-6/n-3 ratio as well as indices of atherogenicity and thrombogenicity, which are critical indicators for the risk of cardiac diseases. The results suggest that while HHP improves bacteriological safety, it can compromise the fatty acid profile and nutritive value of caiman meat, which is rich in polyunsaturated fatty acids.