As one of the most significant global health emergencies, COVID-19 has placed extraordinary demands on healthcare systems worldwide. In India, its widespread transmission has been influenced by the country's diverse climatic conditions, geo-ecological complexity, and dense population. This, vector-borne diseases (VBDs)-including malaria, dengue, kala azar, Japanese encephalitis, and chikungunya-have long posed additional challenges to public health infrastructure. Intriguingly, prior exposure to these diseases may shape immune responses, potentially conferring cross-protection against multiple pathogens. A cross-sectional study aimed at assessing the role of VBDs in COVID-19 incidence and mortality revealed a multifaceted relationship. Prior dengue exposure was linked to an increased risk of SARS-CoV-2 infection and mortality, whereas kala azar, Japanese encephalitis, and chikungunya appeared to have protective influences. Notably, malaria had statistically significant protective effects against both SARS-CoV-2 infection and mortality (p < 0.04). These findings suggest that immune mechanisms-such as cross-reactive antibodies or immune regulation-may alter susceptibility to COVID-19. Given the substantial protective effect of malaria, further investigation is warranted to clarify the underlying biological processes involved. Insights from this study could guide public health strategies, optimize resource allocation, and refine intervention measures in regions where both COVID-19 and VBDs remain major concerns.