Background Nursing is a high-risk profession and nurses’ exposure to workplace risk factors such as heavy workloads and inadequate staffing is well documented. The COVID-19 pandemic has exacerbated nurses’ exposure to workplace risk factors, further deteriorating their mental health. Therefore, it is both timely and important to determine nursing groups in greatest need of mental health interventions and supports. Purpose The purpose of this study is to provide a granular examination of the differences in nurse mental health across nurse demographic and workplace characteristics before and after COVID-19 was declared a pandemic. Methods This secondary analysis used survey data from two cross-sectional studies with samples (Time 1 study, 5,512 nurses; Time 2, 4,523) recruited from the nursing membership (∼48,000) of the British Columbia nurses’ union. Data was analyzed at each timepoint using descriptive statistics and ordinal logistic regression. Results Several demographic and workplace characteristics were found to predict significant differences in the number of positive screenings on measures of poor mental health. Most importantly, in both survey times younger age was a strong predictor of worse mental health, as was full-time employment. Nurse workplace health authority was also a significant predictor of worse mental health. Conclusions Structural and psychological strategies must be in place, proactively and preventively, to buffer nurses against workplace challenges that are likely to increase during the COVID-19 crisis.