The objective was to study the effect of serial night shifts on the cognitive, psychomotor, and moral performance of emergency medicine residents of an academic Emergency Medicine Department. This prospective case-crossover study compared emergency medicine residents' sleep time, subjective sleepiness, cognitive function, moral judgment, and psychomotor skills after 5 consecutive days versus night shifts using sleep diaries, activity monitors, and multiple performance tests. Paired t-tests and Wilcoxon signed-rank tests were used to analyze data based on normality. Correlation analysis was done using Spearman's correlation test. Subgroup analysis was also performed to find any difference based on gender and year of residency. Twenty-seven emergency medicine residents participated (13 males, 48.1%). The distribution across residency years was as follows: 44.4% in their first year, 25.9% in their second year, and 29.6% in their third year. Following five consecutive night shifts, total sleep duration decreased significantly from 338.1 ± 67.8 to 307.4 ± 71.0 min (p < 0.001), while subjective sleepiness scores increased from 9.6 ± 3.3 to 13.6 ± 4.6. Psychomotor performance and reaction times did not significantly differ between night and day shifts. However, working memory declined, assessed by self-paced three-back test scores (median [IQR] 517.1 [471.9-546.7] vs. 457.6 [334.4-508.8]; p = 0.034) and interference test scores (445.5 ± 59.9 vs. 407.2 ± 56.8; p < 0.001), along with moral judgment (median [IQR] 19 [18-28] vs. 15 [11-21]; p = 0.010) after serial night shifts. No correlations existed between performance measures nor differences based on gender or residency year. Residents sleep less following night versus day shifts, reporting the highest sleepiness levels after 5 consecutive nights. Despite this, psychomotor performance and reaction times did not significantly differ. However, considerable reductions occurred in moral judgment, working memory, and interference test performance after serial night shifts.