Hospitals faced extraordinary challenges during the pandemic. Some of these were directly related to patient care—expanding capacities, adjusting services, and using new knowledge to save lives in a dynamically changing situation. Other challenges were regulatory. The COVID-19 pandemic significantly disrupted routine hospital infection control practices. We report the results of an interview study with 13 individuals associated with infection control in a small independent hospital. We employed the Systems Engineering Initiative for Patient Safety (SEIPS) model as a theoretical framework and as a basis to analyze data. The findings revealed how routine practices and protocols were displaced in notable ways. Due to COVID-19, clinical activities were modified, and the increased demands of regulatory reporting became laborious, and punitive if reports were late. Strategies are needed to mitigate increases in healthcare-associated infections. Our examination of the information flows, transformation, and needs shows areas in which digital tool creation and the use of a trained informatics workforce could ameliorate and automate many processes.