The COVID-19 lockdown has been reported as a “ventilator” for the reinstatement of natural resources across the globe. Hence, the present study attempts to evaluate the impact of COVID-19 lockdown on the water quality of River Gomti across its stretch of ~960 km through the assessment of ‘Water Quality Index’ (WQI). The study also highlights the potential risk of faecal-oral transmission of COVID-19 through intake of river water facing the issue of direct discharge of domestic sewage. A deterioration in the water quality was witnessed at ~69% sampling locations during the lockdown period (May 2020). Interestingly, none of the water samples during the pre-lockdown, lockdown, and post-lockdown periods across the whole stretch belonged to the “excellent” category (WQI<25). The DO levels fell across ~69% and ~88% of the sites during the lockdown and post-lockdown periods, respectively. Moreover, there was an increase in the BOD5 levels across ~69% and 75% of the sites during lockdown and post-lockdown periods, respectively. These findings indicate that the release of sewage without or with partial treatment is a chief contributor of water pollution in the groundwater fed River Gomti. Thereby, highlighting the possible risk of faecal-oral transmission of the corona virus, and creating a major concern for the residents across its stretch. The urban sprawl and riverfront development in Lucknow city also emerge as potential causes of water quality deterioration in River Gomti, considering that the water quality at five sites within the city was under the “unfit” category regardless of the lockdown situation. Thus, the urgent need of management of domestic sewage release into the river and further research on the potential risk of faecal-oral transmission of COVID-19 have been suggested in the study.