Nurses are already exposed to plenty of stressors while at work, one of which being the unavoidable nature of rotating shift work scheduling which can have profound physiological effects carrying heightened long-term health risks. Working on the frontlines of the COVID-19 pandemic has introduced new stressors while further exacerbating the effects of pre-existing ones in this already understudied group of essential workers. The purpose of this research was to examine physiological markers of stress and health in nurses during the COVID-19 pandemic. Nine subjects (mean age 32.11 ± 7.25 years) from two hospitals in the Greater Victoria region collected data over an eight-day shift roster consisting of two 12-hour day shifts, two 12-hour night shifts, and four days off in two separate collection periods; remote data collection was used to adhere to COVID-19 safety guidelines. Salimetrics ELISA kits were used to conduct analyses for salivary cortisol, melatonin, and interleukin-6 (IL-6) content. Frequency domain heart rate variability (HRV) was collected with a Polar H10 Chest Strap and Polar Ignite Activity Tracker. A salivary sample and 5-minute HRV recording were obtained upon waking or shortly thereafter on each day; a second saliva sample was obtained after work for the four working days. The Expanded Nursing Stress Scale (ENSS) was completed at the end of the last night shift in each period. There were no significant differences between IL-6 concentrations across the eight days within each period; the same was observed for cortisol. Additionally, no difference was apparent between the morning and evening salivary cortisol concentrations, thus demonstrating a blunting of the diurnal release pattern. Evening salivary cortisol concentrations remained elevated near the level of morning samples and were consistently above reference values for the population age group. Morning salivary melatonin concentrations significantly differed by day (F(5, 25) = 6.626, p < 0.001) but not period; melatonin concentrations were lowest following night shifts, showing a suppression in release due to participants being exposed to light at night with shift work. No statistically significant differences were apparent between any frequency domain HRV parameters in either Period 1 or Period 2. Perceived occupational stress was heightened in comparison to previously published pre-pandemic research using the ENSS. The results of this research reveal alterations to the circadian nature of cortisol and melatonin alongside elevated perceived occupational stress; these physiological and psychological effects can compound the risk for adverse health outcomes. While it is difficult to discern the root cause of these responses, it nevertheless reveals insight into the effects of nurses working during the COVID-19 pandemic and raises concern for potentially related disease risk. / Graduate