This study responds to the need to explore psychological predictors of COVID-19-related anxiety in vulnerable groups. An anonymous voluntary online survey was conducted (n = 520) with (a) working parents with young children (0–12 y.o.), (b) people with chronic physical conditions, (c) people with multiple vulnerability characteristics and (d) a control group (no self-reported vulnerability) in 2022. Findings showed that perceived stress of the parents and trait anxiety of the chronic sufferers were single weak positive predictors of COVID-19 anxiety. However, both psychological factors had a stronger effect on the pandemic-related anxiety for the group with multiple vulnerabilities. In the control group, trait resilience and optimistic expectations (combined with perceived stress) were moderate negative predictors of COVID-19 anxiety. The findings emphasize the importance of perceptions, expectations, trait anxiety as well as the need for intersectional research of vulnerability from multiple perspectives. Furthermore, they highlight the necessity of groupspecific policies and interventions aimed both at handling the negative psychological tendencies of the vulnerable groups and at strengthening the positive tendencies of non-vulnerable groups, rather than tackling only emergent anxiety conditions in crisis times.