Recent research on humans’ prosociality has highlighted the crucial role of Honesty-Humility, a basic trait in the HEXACO personality model. There is overwhelming evidence that Honesty-Humility predicts prosocial behavior across a vast variety of situations. In the present contribution, we cloud this rosy picture, examining a condition under which individuals high in Honesty-Humility reduce prosocial behavior. Specifically, we propose that under self-uncertainty, it is particularly those individuals high in Honesty-Humility who reduce trust in unknown others and become less prosocial. In 5 studies, we assessed Honesty-Humility, manipulated self-uncertainty, and measured interpersonal trust or trust in social institutions using behavioral or questionnaire measures. In Study 1, individuals high (vs. low) in Honesty-Humility showed higher levels of trust. This relation was mediated by their positive social expectations about the trustworthiness of others. Inducing self-uncertainty decreased trust, particularly in individuals high in Honesty-Humility (Studies 2–5). Making use of measuring the mediator (Studies 2 and 3) and applying a causal chain design (Studies 4a and 4b), it is shown that individuals high in Honesty-Humility reduced trust because self-uncertainty decreased positive social expectations about others. We end with an applied perspective, showing that Honesty-Humility is predictive of trust in social institutions (e.g., trust in the police; Study 5a), and that self-uncertainty undermined trust in the police especially for individuals high in Honesty-Humility (Study 5b). By these means, the present research shows that individuals high in Honesty-Humility are not unconditionally prosocial. Further implications for Honesty-Humility as well as for research on self-uncertainty and trust are discussed.