From the last month of 2020, sudden outbreak of novel corona virus caused socio-economic lockdown in many countries. Many studies proved that temporary shutdown of economic sectors helped to recover river water quality. Perhaps, for the first time, this present study is conducted in an industrially and agriculturally influenced catchment of river Damodar, India. This research was fixed some relevant objectives like (i) to evaluate the changes of heavy metals (Zn, Cd, Pb, Ni, Cr and Fe) and microbial contamination (TVC, TC and FC) of river water (ii) to identify the magnitude of human health hazard during lockdown compared to pre lockdown and unlock phase. Total 33 water samples were collected in three periods. During lockdown, TVC, TC and FC showed the gradual decreasing trend in this stretch. All samples exceed the concentration of microbes compared to recommended standard in three periods. Among all heavy metals, Zinc, iron, chromium found their abandoned presence in the river water. Heavy Metal Pollution Index (HPI) showed 100% sample water of highly polluted (HPI > 150) type for drinking and other purpose. During lockdown, HPI showed around 54.54% sample changed to lower pollution and 45.45% changed to medium pollution level. During unlock phase, 45.45% samples again changed to high pollution. Pearson’s correlation coefficient and hierarchical cluster analysis indicated strong relation among heavy metals with fecal coliform in this river. This suggests high possibilities of common source of contamination (wastes of iron and steel plant, chemical plant, cement factories, agricultural runoff, municipal sewages etc) in river bed. No carcinogenic Hazard Index (HI) values of ingestion by children indicated higher potentiality to health risk (HI > 1) in all samples of three periods and during lockdown, 36.36% samples showed no possible health risk for adults (HI < 1). HI of dermal contact showed no possible health risk for children and adults in three periods. This assessment strongly recommended scientific and cheep management techniques to control water pollution and related health hazard in the study area.