Aim: To explore the effect of adjuvant therapy with ω-3 polyunsaturated fatty acids (PUFA) on both, the severity of clinical symptoms and serum concentration of interleukin-1β (IL-1β) in Croatian war veterans diagnosed with post-traumatic stress disorder (PTSD). To determine the ratio of eicosapentaenoic acid (EPA, C20:5ω-3) and docosahexaenoic acid (DHA, C22:6ω-3) in the serum total fatty acid profile, and to determine their individual association with the severity of clinical symptoms of PTSD. Methods: The study included 90 male participants who were randomly assigned into the control group (50 mg of sertraline/day) or into the therapy group (50 mg of sertraline plus two OMEGA-3 capsules (300 mg ω-3 PUFA)/day). Clinician-Administered PTSD Scale (CAPS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale 17 (HAM-D-17) were used to assess the severity of PTSD symptoms. Fatty acid composition of the serum was analyzed by gas chromatography. Determination of IL-1β was conducted by the ELISA method. Data about life-style habits were collected by a structured interview. Structural equation modeling (SEM) was used to assess the causal relationship between variables. The model includes all the variables that are known or presumed to be associated with the process of change in the intensity of PTSD. Multivariate general linear models (GLM) were applied with the aim to evaluate association between plasma fatty acid levels and PTSD severity scales, while controlling for different confounders. Results: Compared to control group the therapy group demonstrated significantly greater improvement in CAPS (P = 0.021) and HAM-A (P < 0.001) clinician-rated scales, while there was no difference for HAM-D scale (P = 0.154). In contrast, there was no evidence of association between IL-1β levels and the severity of clinical symptoms of PTSD (CAPS τ = -0.078, P = 0.499; HAM-A τ = -0.148, P = 0.213; HAM-D τ = -0.068, P = 0.560). Also, no effect of ω-3 augmentation on concentration of IL-1β was noticed. There was no confirmation of effect of ω-3 augmentation on the concentration of IL-1β after the treatment (P = 0.872). EPA made up for 0.1%, and DHA made up for 0,5% of total fatty acids pool. Statistically significant negative correlation was established between EPA level and the severity of PTSD symptoms (CAPS τ = -0.326, P < 0.001; HAM-A τ = -0.304, P = 0.001; HAM-D τ = -0.345, P < 0.001). SEM confirmed that PTSD severity is affected by EPA (Wilks’Λ = 0.763-0.805, P from 0.006 to 0.018, AA/EPA (Wilks’Λ = 0.699-0.757, P = 0.004), and dairy products consumption (Wilks’Λ = 0.760-0.791, P from 0.045-0.088). No other fatty acid ratio or dietary/lifestyle variable was found to significantly affect the severity of PTSD symptoms (P from 0.362 - 0.633). Conclusion: Augmentation of sertraline with -3 PUFA was proved as an effective adjuvant therapy for chronic PTSD in war veterans. The EPA ratio negatively correlated with the intensity of clinical symptoms of chronic PTSD. The study confirmed that lower EPA levels are associated with the severity of clinical symptoms in a combat-related chronic PTSD. EPA level is inversely associated with intensity of PTSD symptoms. According to our findings the EPA serum levels could possibly be used as a categorization biomarker of the severity of combat-related PTSD symptoms. Regardin certain study limitations our results should be considered just on indicative level. Further placebo-controlled studies are necessary to determine effect of ω-PUFA as possible adjunctive therapy in sertraline treated PTSD patients. Cross-over studies will be preferred in order to reduce possible effect of different environmental factors on parameters observed in this study. Also, further well designed longitudinal studies on large sample are necessary to elucidate possible role of EPA in PTSD.