The current study aims to comprehend the effect of the various combinations of 3,4‐dihydroxyphenylacetic acid (3,4‐DHPA) and its esters in varying molar ratios on retarding oxidation in bulk refined fish oil in the presence of 0.3% w/w water. All the esters and 3,4‐DHPA exhibited better performance than the synthetic antioxidant butylated hydroxytoluene. In the presence of trace water, the parent compound was found to have a synergistic effect with hexyl ester when used at a molar ratio of 2:1, respectively, exhibiting a higher percent reduction among all the esters and their combinations. The study also showed that the presence of extraneous water can significantly accelerate the oxidation (twofold) in a bulk fish oil system. This suggests that the microenvironment of the oil is altered when water is present and that association colloids play a key role in enhancing the rate of oxidation. Thus, while designing a competent mixture of antioxidants, the specific site of oxidation involved and the surface‐active components should be taken into consideration to efficiently retard oxidation.Practical Applications: Analyzing the impact of trace amounts of water on the efficiency of natural antioxidants, including 3,4‐DHPA and its lipophilic esters, helps to comprehend the required optimal antioxidant concentrations for such a dynamic bulk oil system. The study finds application in controlling oxidation in PUFA‐rich oils containing surface‐active minor components that can accelerate oxidation. The results of the study show that 3,4‐DHPA and its esters could be a potential replacement for the synthetic antioxidant BHT in all aspects.