Purpose The purpose of this study was to evaluate how the “COVID-19 prevention and control measures” changed nosocomial infections in neurosurgery. Methods To explore changes in nosocomial infections in neurosurgery during the COVID-19 pandemic, the clinical data of inpatients of neurosurgery from January 1, 2020, to April 30, 2020 (COVID-19 era) were first analyzed and then compared with the same period in 2019 (pre-COVID-19 era). We also analyzed data from May 1, 2020, and December 31, 2020 (post-COVID-19 era) at the same time in 2019 (second pre-COVID-19 era). Results The nosocomial infection rate was 7.85% (54/688) in the pre-COVID-19 era and 4.30% (26/605) in the COVID-19 era (P = 0.011). Between the pre-COVID-19 and COVID-19 eras, the respiratory system infection rate was 6.1% vs. 2.0% (P < 0.001) and the urinary system was 1.7% vs. 2.0% (P = 0.837). Between the pre-COVID-19 and COVID-19 eras, the proportion of respiratory system and urinary infections in total nosocomial infections was 77.78% (42/54) vs. 46.15% (12/26) and 22.22% (12/54) vs. 46.15% (12/26), respectively, (P = 0.006). Between the second pre-COVID-19( ) and post-COVID-19 eras, the proportion of respiratory system and urinary infections in total nosocomial infections was 53.7% (44/82) vs. 40.6% (39/96) and 24.4% (20/82) vs. 40.6% (39/96), respectively, (P = 0.022). Conclusions The COVID-19 pandemic reduced the incidence of nosocomial infection in neurosurgery, and the main reduction was in respiratory infection, while the proportion of urinary infections in total nosocomial infections increased significantly.