Global polycrises comprise the synchronous or consecutive occurrence of various crises, with no intervening phases of stability, e.g., coronavirus disease 2019 (COVID-19) pandemic, inflation, war and climate crisis. This poses challenges for both society as a whole and its individual members. Polycrises are associated with enormous psychological stress, especially for vulnerable groups. Polycrises also impair social interaction, which can trigger or intensify subjectively stressful loneliness. The aim of this narrative review is to show how loneliness affects social behavior in times of global polycrises and what the consequences are. Loneliness is associated with both mental and physical morbidity and mortality as well as being a significant barrier to recovery. Studies have shown that there is a mutual detrimental influence between mental illness and loneliness. The social behavior of chronically lonely people is characterized by a negative cognitive bias, hypervigilance in the social context and a dysregulated oxytocin system. Furthermore, the quality and quantity of these relationships are significantly impaired. The social consequences of loneliness are, for example, a decrease in social engagement and low voting participation. The phenomenon of loneliness clearly shows that crises can exacerbate latent problems and bring them to the surface; however, crises should also be seen as an opportunity to openly and constructively address shame-laden topics such as loneliness in public discourse and in psychotherapeutic settings.