Sub-Saharan Africa (SSA) bears a disproportionate and overlapping burden of soil-transmitted helminths (STHs) and sexually transmitted viral infections. An estimated 232 million pre-school and school-aged children in SSA are vulnerable to STH infections. Together with this, SSA has a high prevalence of herpes simplex virus type II (HSV-2), the primary cause of genital herpes. Studies have examined the immunological interactions between STHs and human immunodeficiency virus and human papillomavirus during co-infections. However, epidemiological and immunological studies on STH-HSV-2 co-infections are lacking, therefore their impact on sexual and reproductive health is not fully understood. STH-driven Th2 immune responses are known to downregulate Th1/Th17 immune responses. Therefore, during STH-HSV-2 co-infections, STH-driven immune responses may alter host immunity to HSV-2 and HSV-2 pathology. Herein, we provide an overview of the burden of STH and HSV-2 infections in SSA, and host immune responses to STH and HSV-2 infections. Further, we emphasize the relevance and urgent need for (i) focused research into the interactions between these important pathogens, and (ii) integrated approaches to improve the clinical detection and management of STH-HSV-2 co-infections in SSA.