n-3 Highly unsaturated fatty acids (HUFA), are essential components of neuronal membranes and mediate a range of complex bioactive properties including gene expression, myelination, cell-signalling and dopaminergic function. Deficits in n-3 HUFA have been linked to increased risks for addictive disorders, thus we posited that lower fish consumption would be associated with greater risks for perinatal smoking among 9640 mothers enroled in the Avon Longitudinal Study of Parents and Children. We used univariable and multivariable regression models to examine relationships between self-reported prenatal dietary intakes of n-3 HUFA-rich foods (fish and shellfish) and maternal smoking; outcomes included cessation and the number of cigarettes smoked per d. Both before and during pregnancy, there was consistent evidence (P<0·001) of protective fish intake–smoking associations; relative to mothers reporting no fish consumption, those who reported some fish consumption (<340 g/week) and high fish consumption (340 g+/week) at 32 weeks of gestation showed lower likelihoods of smoking (adjusted P values <0·001). Respective OR for these relationships were 0·87 (95% CI 0·77, 0·97) and 0·73 (95% CI 0·61, 0·86). Although the prevalence of smoking diminished, from a high of 31·6% (pre-pregnancy) to a low of 18·7% (second trimester), the magnitude of fish intake–smoking associations remained stable following adjustment for confounders. These observations suggest that greater fish or n-3 HUFA consumption should be evaluated as an intervention to reduce or prevent smoking in randomised clinical trials.