Africa has a number of climate-sensitive diseases. One that remains a threat to public health is cholera. The aquatic environment temperature is the most important ecological parameter governing the survival and growth of Vibrio cholerae. Indeed, recent studies indicate that global warming might create a favorable environment for V. cholerae and increase its incidence in vulnerable areas. In light of this, a Poisson Regression Model has been used to analyze the possible association between the cholera rates in southeastern Africa and the annual variability of air temperature and sea surface temperature (SST) at regional and hemispheric scales, for the period 1971-2006. The results showed a significant exponential increase of cholera rates in humans during the study period. In addition, it was found that the annual mean air temperature and SST at the local scale, as well as anomalies at hemispheric scales, had significant impact on the cholera incidence during the study period. Despite future uncertainty, the climate variability has to be considered in predicting further cholera outbreaks in Africa. This may help to promote better, more efficient preparedness.