This study explores the intricate relationship between depression, academic stress, and academic performance among secondary school students in Mbita Sub-County, Homa-Bay, Kenya. Depression and academic stress are prevalent issues affecting students worldwide, yet their impact on academic achievement remains a topic of significant concern. The primary objective of this research was to investigate how depression and academic stress influence the academic performance of students in secondary schools within Mbita sub county Homa Bay. A cross sectional study design was employed, involving the administration of standardized questionnaires to a sample of secondary school students. These questionnaires assess levels of depression, academic stress, and academic performance. The study also examines potential demographic or socio-economic factors that may moderate the relationship between these variables. Findings from the research shed light on the prevalence of depression and academic stress among students in Mbita Sub-County, as well as their implications for academic outcomes. Ultimately, the study aimed to inform the development of targeted interventions and support services aimed at addressing mental health issues and improving academic performance among secondary school students in the region.