Background : Bloodstream infections (BSI) due to opportunistic microbes in the coronavirus disease 2019 (COVID-19) pandemic lead to high morbidity and mortality among hospitalized patients. Thus, it is vital to find out the risk factors of BSI and to learn the ways to mitigate it. Aim : The aim of this study was to evaluate important risk factors of BSI due to opportunistic pathogens and to assess the role of the rigid infection control program to deal with this issue. Methods : A prospective, cross-sectional study was performed for 6 months on 150 patients admitted in both COVID-19 and non-COVID-19 intensive care units of our hospital. BSI was confirmed by the BACTEC and Vitek 2 compact system. Prospective surveillance and environmental sampling were carried out for source tracking along with rigorous infection control measures and the outcome was analyzed. Findings : Burkholderia cepacia, Elizabethkingia meningoseptica, Candida auris, vancomycin-resistant Enterococcus , and Achromobacter xylosoxidans were the common opportunistic pathogens isolated from a single or paired blood sample(s) in our study. Key risk factors were prolonged intensive care unit stay, central venous access, mechanical ventilation, immune-compromised condition, and use of biologics. Reverse osmosis water and used normal saline bottles were the common environmental source of infection. Following the implementation of precise infection control measures, there was a sharp decline in BSI cases, which was not attributed to the downfall of COVID-19 cases. Conclusion : Combined prospective surveillance and environmental sampling helped to find out the sources and implementation of an intensive and insistent infection control program that are needed to control opportunistic pathogens mediated BSI.