Abstract Background Mass outbreaks such as pandemics are associated with mental health problems requiring effective psychological interventions. Although several forms of psychological interventions may be advocated or used, some may lack strong evidence of efficacy and some may not have been evaluated in mass infectious disease outbreaks. This paper reports a systematic review of published studies (PROSPERO CRD:42020182094. Registered: 24.04.2020) examining the types and effectiveness of psychological support interventions for the general population and healthcare workers exposed to mass infectious disease outbreaks. Methods A systematic review was conducted. Randomised Controlled Trials (RCT) were identified through searches of electronic databases: Medline (Ovid), Embase (Ovid), PsycINFO (EBSCO) and the Cochrane Library Database from inception to 06.05.2021 using an agreed search strategy. Studies were included if they assessed the effectiveness of interventions providing psychological support to the general population and / or healthcare workers exposed to mass infectious disease outbreaks. Studies were excluded if they focused on man-made or natural disasters or if they included armed forces, police, fire-fighters or coastguards. Results Twenty-two RCTs were included after screening. Various psychological interventions have been used: therapist-guided therapy (n = 1); online counselling (n = 1); ‘Emotional Freedom Techniques’ (n = 1); mobile phone apps (n = 2); brief crisis intervention (n = 1); psychological-behavioural intervention (n = 1); Cognitive Behavioural Therapy (n = 3); progressive muscle relaxation (n = 2); emotional-based directed drawing (n = 1); psycho-educational debriefing (n = 1); guided imagery (n = 1); Eye Movement Desensitization and Reprocessing (EMDR) (n = 1); expressive writing (n = 2); tailored intervention for patients with a chronic medical conditions (n = 1); community health workers (n = 1); self-guided psychological intervention (n = 1), and a digital behaviour change intervention (n = 1). Meta-analyses showed that psychological interventions had a statistically significant benefit in managing depression (Standardised Mean Difference [SMD]: -0.40; 95% Confidence Interval [CI]: − 0.76 to − 0.03), and anxiety (SMD: -0.72; 95% CI: − 1.03 to − 0.40). The effect on stress was equivocal (SMD: 0.16; 95% CI: − 0.19 to 0.51). The heterogeneity of studies, studies’ high risk of bias, and the lack of available evidence means uncertainty remains. Conclusions Further RCTs and intervention studies involving representative study populations are needed to inform the development of targeted and tailored psychological interventions for those exposed to mass infectious disease outbreaks.