Higher acuity levels in COVID-19 patients and increased infection prevention and control routines have increased the work demands on nurses. To understand and quantify these changes, discrete event simulation (DES) was used to quantify the effects of varying the number of COVID-19 patient assignments on nurse workload and quality of care. Model testing was based on the usual nurse-patient ratio of 1:5 while varying the number of COVID-19 positive patients from 0 to 5. The model was validated by comparing outcomes to a step counter field study test with eight nurses. The DES model showed that nurse workload increased, and the quality of care deteriorated as nurses were assigned more COVID-19 positive patients. With five COVID-19 positive patients, the most demanding condition, the simulant-nurse donned and doffed personal protective equipment (PPE) 106 times a shift, totaling 6.1 hours. Direct care time was reduced to 3.4 hours (-64% change from baseline pre-pandemic case). In addition, nurses walked 10.5km (+46% increase from base pre-pandemic conditions) per shift while 75 care tasks (+242%), on average, were in the task queue. This contributed to 143 missed care tasks (+353% increase from base pre-pandemic conditions), equivalent to 9.6 hours (+311%) of missed care time and care task waiting time increased to 1.2 hours (+70%), in comparison to baseline (pre-pandemic) conditions. This process simulation approach may be used as potential decision support tools in the design and management of hospitals in-patient care settings, including pandemic planning scenarios.