The objective of the study is to investigate the effect of nutritional supplementation with eicosapentaenoic acid (EPA)-enriched formula on the inflammatory profile of patients with oral cavity cancer. The study was conducted with 53 patients with oral cavity cancer in antineoplastic pretreatment who were randomized into two groups: the control group received a powdered supplement without EPA during 4 wk and the intervention group received a liquid supplement enriched with EPA (2 g/day) during the same period. In the baseline and after 4 wk of supplementation, serum concentrations of albumin, prealbumin, C-reactive protein (CRP), and interleukin-6 (IL-6) were measured. Values of CRP and of CRP/albumin ratio were lower in the intervention group than those in the control group. However, when the two groups were compared to each other after intervention, any significant difference was not observed. There was a significant negative correlation between levels of CRP and albumin, and IL-6 and albumin, both in the control and in the intervention groups. In both groups, a positive correlation between concentrations of IL-6 and CRP was observed. No significant difference was encountered in the assessed parameters between the group that received standard supplement and the group that received EPA-enriched supplement.