Higher indoor particulate matter (PM) concentrations are linked with increased asthma morbidity. Dietary intake of fatty acids, also linked with asthma outcomes, may influence this relationship. To determine the relationship between omega-3 and omega-6 fatty acid intake and pediatric asthma morbidity, and the association between fatty acid intake and strength of indoor, PM-related asthma symptoms, albuterol use, and systemic inflammation. Analyses included 135 children with asthma enrolled in the AsthmaDIET Study. At baseline, 3 months, and 6 months, data included: week-long average home indoor concentration of PM ≤2.5 μm in aerodynamic diameter and PM ≤10 μm in aerodynamic diameter, dietary intake of omega-3 and omega-6 fatty acids, daily symptoms, and peripheral blood leukocytes. Asthma severity and lung function were assessed at baseline. Multivariable regression models, adjusted for known confounders, were used to determine associations between each fatty acid and outcomes of interest, with interaction terms (fatty acids × PM) in longitudinal analyses. Higher omega-6 intake associated with increased odds of increased asthma severity (  = 0.02), and lower FEV /FVC ratio (  = 0.01). Higher omega-3 intake associated with reduced effect of indoor PM ≤2.5 μm in aerodynamic diameter on symptoms (  < 0.01), whereas higher omega-6 intake associated with amplified effect of indoor PM ≤2.5 μm in aerodynamic diameter on symptoms and circulating neutrophil percentage (  < 0.01). Omega-3 and omega-6 intake are associated with pediatric asthma morbidity and may modify the asthmatic response to indoor PM.