Purpose: The study aimed at presenting a comparative appraisal of the trends of the two most prevalent infectious diseases bedeviling the region: human immunodeficiency virus (HIV) and tuberculosis (TB). Subject & Methods: Data on fourteen ECOWAS member countries and also fourteen member countries of the SADC bloc. This represents about 93.3% and 87.5% membership of the ECOWAS and SADC blocs respectively. Although the choice of sample size is determined largely by the availability of data, the choices were carefully made to maximize available observation. The data were sourced from World Development Indicators online database published by the World Bank. We use two measures of infectious diseases: the prevalence rate of human immunodeficiency virus and the incidence of tuberculosis. Results: The HIV prevalence rates and incidence of TB were uneven in the two selected trade blocs. The magnitude and the severity of the diseases varied. The burden of both diseases was higher for SADC and lesser for ECOWAS. The average prevalence rate of HIV in the SADC bloc over the study period was 600% of the prevalence rate in ECOWAS (SADC = 12.5%, ECOWAS = 2.1%). Likewise, in the same period, the average TB incidence per 100,000 people was 578.8 and 181.7 respectively in the SADC and ECOWAS blocs. Conclusions: The study finds that the magnitude and severity of the diseases vary widely between the Economic Community of West Africa States (ECOWAS) and the Southern Africa Development Community (SADC) trade blocs. And, while concerted efforts at curbing the diseases have yielded results, there is still much to be done in both blocs.