We established the 2019 Rio Grande birth cohort to investigate the life course epidemiology of mental health and its intergenerational transmission. In 2019, we systematically identified all hospital births in the city of Rio Grande, located in Southern Brazil. Mothers who delivered a singleton liveborn child were administered a standardized, face-to-face questionnaire. In 2020, we conducted 2 follow-up assessments (WebCOVID-19 1 and 2), a third in 2021-22 (WebCOVID-19-3), and a fourth in 2023-24 (WebPOST-COVID). Across these follow-ups, we collected data on socio-demographic, environmental, and behavioral factors pertaining to both mother and child, as well as maternal mental health. Child mental health and development were specifically evaluated during the fourth follow-up. At baseline, 2,051 mothers were interviewed. Response rates for the online follow-ups were 54.1%, 51.1%, 48.7%, and 34.6%, respectively. In WebCOVID-19-3, the highest prevalence rates for depression (34.7%) and anxiety (33.1%) were observed. This cohort provides novel insights into maternal mental health, child development, and post-coronavirus disease 2019 behaviors, emphasizing culturally specific risk factors. Our findings are based on both published and ongoing studies. Data may be requested upon reasonable request.