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Background Mental disorders are currently the greatest global health burden. The coronavirus diseases 2019 (COVID-19) pandemic is having an adverse impact on people's mental health, particularly in vulnerable populations, such as refugees. Aims The present study was designed to examine the association between COVID-19 and changes in mental health in Syrian refugees in Turkey. Method We conducted a two-wave panel survey of a representative sample of 302 of the estimated 500 000 Syrian refugees (ages 18 and older) living under humanitarian support in Istanbul (first wave between 9 and 15 July 2020 and the follow-up between 11 and 14 September 2020). We administered seven items from the CoRonavIruS Health Impact Survey in addition to one-context specific item about life changes because of COVID-19, and measures of depression (10-item Center for Epidemiologic Study Depression Scale, CESD-10), anxiety (6-item State-Trait Anxiety Inventory, STAI-6) and perceived stress (Perceived Stress Scale, PSS-4). Results A factor analysis yielded three COVID-19 factors, labelled ‘social relationships’, ‘stress’ and ‘hope.’ We conducted a series of cross-lag panel analyses to test associations between the COVID-19 factors and mental health. We found associations between all COVID-19 factors and CESD-10, between COVID-19 ‘stress’ and STAI-6, and between COVID-19 ‘stress’ and COVID-19 ‘hope’ and PSS-4. Conclusions Our measures of life changes because of the COVID-19 pandemic are associated with changes in the mental health of Syrian refugees living in Istanbul. It is therefore important that they are provided with services to reduce what may be particularly debilitating consequences of COVID-19.