The impact of COVID-19 lockdown on the absolute concentration of air pollutant has been widely investigated, whereas the impact of lockdown on global shipping-related air pollutants still remained poorly understood because the contribution of individual source cannot be observed directly. In our study, we employed an efficient chemical transport model (GEOS-Chem) to quantify the shipping-related PM2.5, NO2, and O3 levels in early 2019 and 2020, and assessed the impact of COVID-19 lockdown on global shipping-related air pollutants and health effects. The result suggested that shipping-related global PM2.5, NO2, and O3 levels reduced by 14%, 85%, and 1%, respectively. Furthermore, the decreasing ratios of air pollutants in difference regions often suffered from large spatial discrepancy. PM2.5 and NO2 levels in China, India, Europe, and the United States decreased by 6.5% (NO2: 9%), 7.4% (8%), 11% (8.6%), and 15% (10%), which could be caused by dense shipping activities during the non-lockdown period. For O3 concentrations, the shipping-related concentrations in China, India, Europe, and the United States showed 0.7%, −12.9%, 16.6%, and −4.8% during lockdown period, respectively. The relatively slight O3 reduction might be linked with more significant decrease of NOx emission than VOCs. The changes of air pollutant concentrations inevitably led to the variations of health benefits. Globally, the all-cause mortalities caused by shipping-related PM2.5 exposures reached 40,464 (95% CI: 26,546, 54,382) and 39,035 (95% CI: 25,135, 52,935) cases in early 2019 and 2020, respectively. The combined health benefits of PM2.5, NO2, and O3 linked with shipping emission reduction in China, India, Europe, and the United States reached 476 (95% CI: 131, 822), 3341 (95% CI: 3,177, 3505), 2194 (95% CI: −970, 5358), and 311 (95% CI: 242, 379), respectively. Our study confirms the potentially considerable effects of shipping emission on multiple air pollutants and health impacts, which could provide valuable information for air quality management.