A bstract Background and aim The coronavirus disease-2019 (COVID-19) pandemic is a global threat spreading like a wildfire and taking the world by its storm. It has challenged the healthcare delivery systems and disrupted them in a way no one ever imagined before. We at Apollo Hospitals, Chennai, Tamil Nadu, India received many patients in the COVID critical care unit (CCU) and found a gradual lack of bundle care compliance resulting in an upsurge of central line-associated bloodstream infection (CLABSI) amid the patients. Materials and methods A qualitative research approach and quasi-experimental research design were selected to assess the knowledge of the 150 frontline COVID CCU nurses regarding the CLABSI bundle and its prevention strategies. Results This study revealed that 57% [mean (M) = 12.6; standard deviation (SD) = 2.37] of nurses had inadequate knowledge of the CLABSI bundle and its prevention strategies, in the pretest and scored 80% (M = 6.7; SD = 2.28) in the post-test, with “ t ” = 22.06 at p < 0.00001 after the hands-on training. The percentage of compliance to CLABSI bundle care increased to 83% and thereafter in an increasing trend. This was clearly evident through the reduction in the preventable CLABSI rate among critically ill COVID-19 patients. Conclusion Nurses are on the frontline in preventing and controlling healthcare-associated infections (HAIs). Fighting with all the visible and invisible challenges, our research focused on hands-on training for frontline warriors to adhere to the CLABSI bundle care which drove us to the reduction in preventable CLABSI rate in our hospital through improved CLABSI bundle compliance. How to cite this article Premkumar S, Ramanathan Y, Varghese JJ, Morris B, Nambi PS, Ramakrishnan N, et al . “Nurse—The Archer” Fighting Against the Hidden Enemy. Indian J Crit Care Med 2023;27(4):246–253.