Depression is the leading cause of disease burden among women. Recent evidence indicates that inflammation is associated with depression, and factors that contribute to inflammation can be addressed through nutritional and lifestyle interventions. Vitamins B6 and D have been linked with depression and have established roles in inflammation, yet their associations with depression in the presence of low-grade inflammation remain unknown. The purpose of this research was to investigate how high sensitivity C-reactive protein (hs-CRP), a biomarker of inflammation, contributes to different dimensions of depression and to determine to what degree inflammation affects the association between vitamins B6 and D and depression symptoms among women. We carried out a secondary data analysis of non-pregnant women ages 18-44 from the National Health and Nutrition Examination Survey 2005-2008. Depression scores were calculated based on the Patient Health Questionnaire-9 (PHQ-9) and categorized into total depression, somatic depression and non-somatic depression. High depression score (PHQ-9≥10) use was also used as an outcome, as well as individual symptoms of depression. Hs-CRP was associated with higher depression scores among underweight women (B6, as serum pyridoxal-5'phosphate (PLP), was categorized as deficient (<20nmol/L), insufficient (20-29.9nmol/L) or normal (≥30nmol/L). Among those with moderate inflammation (hs-CRP 3-10mg/L), the prevalence of high depression score was highest among women with vitamin B6 deficiency (20%), followed by those with insufficiency (10%) and those with normal B6 status (5%; p-trend=0.02). In multivariable models, vitamin B6 <30nmol/L was associated with higher odds of experiencing suicidal ideation (OR: 7.33, p=0.01 and OR: 3.5, p=0.06 for B6 deficiency and insufficiency, respectively) and depressed mood (OR: 3.12, p=0.004 for B6 insufficiency). Suboptimal vitamin D concentration (<75nmol/L) was significantly associated with higher odds for depression among women who had elevated CRP (OR: 6.55, p=0.02 and OR: 9.54, p=0.001 for 25-OHD<75nmol/L and 25-OHD<50nmol/L, respectively). Together, the results of these studies suggest that inflammation may be interacting with micronutrient deficiencies, and contributing to different symptoms or severities of depression. Nutritional and lifestyle interventions that reduce inflammation could be used to prevent or treat depression among women of reproductive age.