Depression affects over 280 million people worldwide. Long-chain omega-3 fatty acids may relate to depression, but observational evidence is inconsistent.

To examine the association between dietary long-chain omega-3 intake and depression severity in US adults.

Cross-sectional analysis of NHANES 2021–2023. Participants: Adults ≥18 years with complete dietary, PHQ-9, and covariate data (n=3,608). Main outcome: PHQ-9 severity categories (0–4 to 20–27). Exposure: Total omega-3 (ALA, EPA, DPA, DHA) from 24-hour recalls (FNDDS 2021–2023); supplements excluded. Supplement use was a binary covariate.

Survey-weighted ordinal logistic regression (svyolr); all continuous variables centred/scaled (ORs per 1 SD). Covariates: age, sex, race/ethnicity (collapsed for sparse cells), income-to-poverty ratio, BMI, smoking, alcohol, physical activity, omega-3 supplement use. Results: Higher total omega-3 intake was inversely associated with depression severity (OR 0.865 per 1 SD, 95% CI 0.761–0.983, p=0.026). EPA showed a significant inverse association (OR 0.907, 95% CI 0.824–0.998, p=0.045); ALA, DPA, and DHA were not significant. No interaction by sex (p=0.656) or race/ethnicity (p=0.155). Sensitivity analyses: excluding supplement users (n=3,093) OR 0.872 (95% CI 0.773–0.984, p=0.026); two recalls only (n=3,229) OR 0.847 (95% CI 0.751–0.955, p=0.007).

Dietary omega-3 intake, particularly EPA, was modestly and inversely associated with depression severity. Residual confounding and reverse causation remain possible; longitudinal studies with biomarkers are needed.