We probe the effects of the COVID-19 lockdown on business activities in China by exploiting big data on 1.5 billion sales invoices. Using a difference-in-differences approach, we estimate that the average drop in sales is between 23% and 35%, depending on firm size, for the 12-week period after Wuhan’s lockdown. The unprecedented plunge in countrywide economic activities is more evident in the first eight weeks, and firm sales gradually resume to 85% of the normal level afterward. Firms in industries requiring more intensive face-to-face interactions suffer more during the public health measures. Also, cities relying on investment-driven economic growth are more resilient. Lastly, local governments’ economic stimulus policies, aimed at alleviating financial losses for small and micro firms, are actually more effective for medium-sized and large firms. Our results provide implications for other economies seeking to develop strategies to contain the disease and reopen the economy.