Background <p>Teaching standard precautions during undergraduate courses in health-related fields is essential for preventing healthcare-associated infections (HAI).</p> Purpose <p>To analyze the effect of an educational intervention on nursing students’ knowledge of COVID-19, standard precautions (SP), transmission-based precautions, and compliance with SP, as well as the factors associated with knowledge.</p> Methods <p>A quasi-experimental pre- and post-test study was conducted with 80 nursing students at a higher education institution in the state of São Paulo, Brazil. The group received an intervention using combined teaching methods, including an interactive lecture, a video presentation, and an instructor-led demonstration of donning and doffing personal protective equipment (PPE).</p> Results <p>Regarding knowledge, after the educational intervention, an increase in correct answers was observed in 14 questions related to COVID-19 and SP measures, with seven showing statistically significant differences. In terms of SP compliance, significant improvements were observed in the following aspects: using alcohol-based products for hand hygiene, proper disposal of sharps containers, discarding PPE in designated locations, protecting wounds or injuries with waterproof dressings before patient contact, wearing gowns/aprons when exposed to bodily fluids, and disposing of contaminated materials in white plastic bags. No factors were found to be associated with knowledge or participant characteristics regarding COVID-19 training.</p> Conclusions <p>The educational intervention proved to be an effective strategy for enhancing nursing students’ knowledge of COVID-19, SP measures, and compliance with SP.</p>