Meat and fish have varying contents of haem-Fe and polyunsaturated fatty acids (PUFAs) and are hence sensitive to oxidation during its preparation and gastrointestinal digestion. However, studies comparing the sensitivity of meat and fish to oxidation during digestion are scarce. In this experiment, we measured 4-HHE and 4-HNE following the preparation and in vitro digestion of a red meat product (pork), white meat (chicken), a fatty fish (salmon) and a lean fish (cod). Secondly, we investigated if the formation of these compounds in pork is inhibited by nitrite-curing (nitrite salt added at 20 g/kg), or by seasoning with Provencal herbs (added at 10 g/kg). All meats and fish were purchased as fresh as possible and cooked for 70 min in a warm water bath at 70°C. Fatty acids (FA) were analyzed by GC according to Raes et al. (2001). In vitro gastrointestinal digestion was performed with 5 replicates per sample according to Van Hecke et al. (2014). Following their reaction with cyclohexanedione, 4-HHE and 4-HNE in cooked meats and digests were measured by HPLC. The salmon had the highest contents of PUFA (4.43 g/100g), with approximately equal contributions of n-3 and n-6 PUFA. In contrast, chicken and pork had 9.5- to 13-fold lower levels of n-3 PUFA (0.15 g/100g) than n-6 PUFA (1.43 and 1.95 g/100g respectively), whereas n-3 PUFA were the most abundant FA in cod (0.27 g/100g), amounting 6-fold higher than the n-6 PUFA (0.04 g/100g). Of all meats and fish prior to digestion, salmon had the highest 4-HHE levels (8.34 ± 0.97 AUC×10^3/g) followed by pork, chicken and cod (2.39 ± 0.14, 1.89 ± 0.15 and 1.09 ± 0.41 AUC×10^3/g respectively). In contrast, 4-HNE was highest in pork (4.72 ± 0.52 AUC×10^3/g) followed by chicken, and the lowest values were detected in salmon and cod (1.86 ± 0.05, 0.51 ± 0.13 and 0.37 ± 0.27 AUC×10^3/g respectively). Following in vitro gastrointestinal digestion, salmon digests contained the highest levels of 4-HHE (23.5 ± 3.1 AUC×10^3/mL) with 4-HNE concentrations among the lowest (1.93 ± 0.29 AUC×10^3/mL). In contrast, pork digests contained the highest levels of 4-HNE (11.1± 1.6 AUC×10^3/mL) with 4-HHE concentrations among the lowest (3.17 ± 0.13 AUC×10^3/mL). Compared to pork, chicken digests had 30% less 4-HNE and approximately equal 4-HHE concentrations (2.80 ± 0.29 AUC×10^3/mL). Compared to pork and chicken, cod digests had higher 4-HHE levels (5.77 ± 0.56 AUC×10^3/mL) with negligible 4-HNE concentrations (0.69 ± 0.02 AUC×10^3/mL). Both seasoning of the pork with Provencal herbs or nitrite-curing decreased 4-HHE (5-8-fold respectively) and 4-HNE (9-14-fold respectively) levels in the meat prior to digestion. Also, after digestion, 4-HNE levels remained low (0.59 ± 0.28 and 0.42 ± 0.08 AUC×10^3/mL respectively) and 4-HHE was below the detection limit. This study showed 4-HHE to be present in higher concentrations in fish digests, whereas meat digests contained more 4-HNE, which formation can be inhibited by antioxidants.