Canned fish is submitted to processes that may degrade its lipids and form harmful compounds called cholesterol oxidation products (COPs). Samples of Brazilian commercial canned tuna were analyzed to evaluate the influence of different liquid mediums (oil and brine) on the fatty acid composition and formation of COPs. The exchange between fish lipids and the constituents of the covering liquid was highlighted by the high levels of linoleic acid found in tuna conserved in oil. High amounts of COPs were found. However, higher contents of COPs were found in tuna in brine (933.14 to 1914.23 µg/g) than in oil (698.24 to 1167.88 µg/g). This result was mainly promoted by the presence of pro-oxidant elements such as salt, as well as greater heat transfer in brine than in oil. This study showed that canned tuna is a potential source of exogenous COPs, indicating the role of liquid mediums in oxidative processes.