The aim of this study was to establish microbial and heavy metal pollution of the Sava River at three locations close to industry and urban areas (Šabac, Obrenovac, Beograd) in Serbia. Heavy metal analysis included Cu, Zn, Pb, and Cd in the river water and sediment samples. Using the microbiological analysis we tried to establish the effectiveness of total coliforms, faecal coliforms and Escherichia coli in detecting pollution of surface waters. We found that E. coli levels steadily increased downstream from Šabac (location 1; 2100 MPN per 100 mL) to Belgrade (location 3; 10000 MPN per 100 mL). To prevent bacterial contamination, it is necessary to reduce the discharge of wastewater with faecal matters near highly populated towns. Heavy metal levels in sediments correlated with those in the river water. Fluctuations attributed mainly to anthropogenic sources were not high. These results point to acceptable anthropogenic contribution to heavy metal content in the Sava River and to low environmental risk.