Microbial water contamination is a risk for human health, as it causes waterborne diseases like diarrhea. E. coli is a faecal indicator microorganism. Climate variables, such as temperature and precipitation, influence E. coli concentrations in surface and drinking water resources. We measure and statistically analyse E. coli concentrations in drinking and surface water in the Kabul River Basin. E. coli concentrations are very high in the basin. Drinking and bathing water standards are violated. Water temperature, surface air temperature, discharge and precipitation were positively correlated with E. coli concentrations. Precipitation induced runoff transports of E. coli from agricultural lands to Kabul River and high temperature coincides with high precipitation and discharge. A linear regression model was developed to assess the net effect of the climate variables on E. coli concentrations. We found that climate variables accounted for more than half of the observed variation in E. coli concentrations in surface (R2 = 0.61) and drinking water (R2 = 0.55). This study indicates that increased precipitation together with higher surface air temperature, as expected in this region with climate change, were significantly correlated with increased E. coli concentrations in the future. Waterborne pathogens are expected to respond similarly to hydro-climatic changes, indicating that disease outbreaks could well become more frequent and severe.