Τhe COVID-19 pandemic has mental health implications for both healthcare workforces and general population, particularly in regions heavily hit by the crisis. Τhe study aimed (i) to investigate anxiety- and depression severity differences between staff of a COVID-19 treatment unit (N = 84) and a hospital without such a unit (N = 55) in comparison to participants of a convenience general population online survey (N = 240) and (ii) to explore relations between such symptoms and hospital staff reaction to COVID-19 in a low COVID-19 burden setting. Anxiety was studied with the Generalized Anxiety Disorder 7-Item in hospital workforces and with the Hospital Anxiety Depression Scale (HADS) in online survey participants. Depression symptoms were assessed with the Patient Health Questionnaire-9 in hospital employees and the HADS in the online survey sample. Symptoms were classified as absent/minimal, borderline abnormal or indicating clinical caseness. Staff reaction to COVID-19 was tapped with a 9-item-questionnaire and the 22-item Impact of Event Scale-revised (IES-R). Proper tests for differences and stepwise ordered logistic regression models were employed. Anxiety- and depression severity was higher in hospital workforces than in online survey participants (P < 0.05). Anxiety was more severe in frontline- compared to backstage employees (P < 0.001) was inversely correlated with age (P = 0.011) and positively with avoidance (P = 0.028). Both anxiety and depression symptoms related to intrusion symptoms (P < 0.001). Regarding the relatively long data collection period, an inverse association between crisis duration and depression symptoms was detected (P = 0.025). These observations point to the urgent need for distress-mitigating interventions for hospital workforces even in low COVID-19 burden settings.