One key factor that appears to be crucial in the rejection of quarantines, isolation and other social controls during epidemic outbreaks is trust—or rather distrust. Much like news reporting and social media, popular culture such as fictional novels, television shows and films can influence people’s trust, especially given that the information provided about an epidemic disease is sometimes seen as grounded in ‘scientific fact’ by societies. As well as providing information on the ‘correct science’ behind disease transmission, spread and illness in films and literature, popular culture can also inform societies about how to feel and how to react during epidemics—that is to say create some expectations about the kinds of societal responses that could potentially occur. In this article we closely analyse three films that centre around epidemic diseases—Contagion (Steven Soderbergh, 2011), Blindness (Fernando Meirelles, 2008) and The Painted Veil (John Curran, 2006)—in order to highlight three categories of distrust that have recently been identified and conceptualised in broader discussions regarding trust and health: institutional, social and interpersonal. These films raise two key issues about trust and social responses during epidemics. First, while certain aspects of trust are badly diminished during epidemic disease outbreaks, epidemics can also interact with pre-existing structural inequalities within society—based on race, gender or wealth—to create mixed outcomes of discord, prejudice and fear that coexist with new forms of cohesion. Second, the breakdown in trust seen at certain levels during epidemics, such as at the institutional level between communities and authorities or elites, might be mediated or negotiated, perhaps even compensated for, by heightened solidity of trust at the social level, within or between communities.