Amid the COVID-19 pandemic, authorities worldwide imposed coercive regulations aimed at curbing the virus’s spread, often at the expense of individuals who were considered potential threats to public health. We argue that individual differences in their support for such actions can be understood from the perspective of an evolved “behavioral immune system”. We conducted two studies within the context of the “zero-COVID” policy in Mainland China. Study 1 recruited 819 Shanghai residents during a strict citywide lockdown and found that individuals’ collectivistic orientation and personal control over their lives predicted their tolerance of injustices involved in disease-control measures. Moreover, the effect of psychological collectivism was enhanced by personal control. Study 2 (N = 403) partly replicated these findings using hypothetical scenarios related to various fictitious viruses. Notably, the effects found in Study 1 only manifested in scenarios involving ambivalent pathogens, which are seldom fatal but highly contagious. Building on the functional flexibility principle of the behavioral immune system theory, we discussed the unique role of ambivalent pathogen signals in generating within-society variability and fine-tuning behavioral immune responses.