BackgroundGrowing evidence suggests that meal timing may influence dietary choices and mental health. Thus, this study examined the association between macronutrient consumption quality, food source, meal timing, and depression prevalence in Americans. Methods23,313 National Health and Nutrition Survey participants from 2007 to 2016 were included in this cross-sectional study. Macronutrient intake was calculated for all day, dinner, and breakfast and subtypes into 4 classes. Based on the Patient Health Questionnaire, depression was defined as a 9-item score ≥ 10 on the PHQ-9. The correlation between macronutrients and depression prevalence was estimated with multivariable logistic regression models and isocaloric substitution effects. ResultsLow-quality carbohydrates (OR = 1.54, 95 % CI: 1.11, 2.12) were positively linked to depression compared with the lowest quartile, after adjusting for age and other covariates. In contrast, total high-quality carbohydrate (OR = 0.52, 95 % CI: 0.40, 0.66), total animal protein (OR = 0.60, 95 % CI: 0.45, 0.80), and total vegetable protein (OR = 0.61, 95 % CI: 0.43, 0.85) were negatively associated with depression was negatively associated. Replacing low-quality carbohydrates with high-quality carbohydrates throughout the day reduced the risk of depression by approximately 15 %. LimitationsCross-sectional data. ConclusionAll in all, diet plays a crucial role in the prevention and treatment of depression. Especially in terms of macronutrient intake, high-quality, moderate intake can reduce the risk of depression. However, different subtypes of macronutrient consumption may have different effects on depression, so it becomes crucial to carefully consider the selection and combination of macronutrients.