Water contamination due to microorganisms poses a risk for human health, as it can cause waterborne diseases, such as diarrhoea. Hydro-climatic variables, such as temperature, precipitation and discharge influence E. coli concentrations in surface and drinking water resources. The net impact of these variables is unclear. Although some recent studies have focused on this topic, these were mostly based in developed countries. Similar studies in developing countries are lacking. In this study we assess the impact of hydro-climatic variables on E. coli concentrations of the Kabul river in Pakistan. This river floods every year. In total 700 biweekly samples were collected and tested for E. coli. Nine sampling sites were located along the river and five drinking water sites from Nowshera were sampled for the period April 2013-September 2015. Surface water samples exceed bathing water standards, while drinking water samples exceed drinking water guidelines; the water is grossly polluted. Water temperature, surface air temperature, discharge and precipitation correlate positively with E. coli concentrations. Increased runoff transports microbes from agricultural lands to Kabul river and high temperatures coincide with high precipitation and discharge. A linear regression model was developed to assess the net effect of the climate variables on E. coli concentrations. This model had coefficients of determination (R 2) of 0.61 for surface and 0.55 for drinking water samples. This suggests that climate variables account for more than half of the observed variation in E. coli concentrations in surface and drinking water. This study indicates that increased precipitation together with higher surface air and water temperature, as is expected in this region with climate change, likely increases E. coli concentrations. Waterborne pathogens are expected to respond similarly to these climate changes, indicating that disease outbreaks could well become more frequent in the future.