In the global crisis of the COVID-19 pandemic, many countries attempt to enforce new social norms to prevent the further spread of the coronavirus. A key to the success of these measures is the individual adherence to norms that are collectively beneficial to contain the spread of the pandemic. However, individuals’ self-interest bias (i.e., the prevalent tendency to license own but not others’ self-serving acts or norm violations) can pose a challenge to the success of such measures. The current research examines COVID-19-related self-interest bias from a cross-cultural perspective. Two studies ( N = 1,558) sampled from the United States and China consistently revealed that participants from the United States evaluated their own self-serving acts (exploiting test kits in Study 1; social gathering and sneezing without covering the mouth in public in Study 2) as more acceptable than identical deeds of others, while such self-interest bias did not emerge among Chinese participants. Cultural underpinnings of independent versus interdependent self-construal may influence the extent to which individuals apply self-interest bias to justifications of their own self-serving behaviors during the pandemic.