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Objective To assess the association between flooding/repeat flooding and: (1) psychological morbidity (anxiety, depression, post-traumatic stress disorder (PTSD)) and (2) health-related quality of life (HRQoL) at 6 months post-flooding. Design Cross-sectional analysis of data from the English National Study of Flooding and Health. Setting Cumbria, England. Participants Questionnaires were sent to 2500 residential addresses at 6 months post-flooding; 590 people responded. Outcomes Probable depression was assessed using the Patient Health Questionnaire, probable anxiety using the Generalised Anxiety Disorder scale and probable PTSD using the short-form PTSD checklist (PCL-6). HRQoL was assessed using the EQ-5D-5L. Mental health outcomes were analysed using logistic regression; HRQoL dimensions using ordinal regression; and summary index/Visual Analogue Scale scores using linear regression. Results One hundred and nineteen participants had been flooded, over half of whom were experiencing a repeat flooding event (54%; n=64). Mental health outcomes were elevated among flooded compared with unaffected participants (adjusted OR for probable depression: 7.77, 95% CI: 1.51 to 40.13; anxiety: 4.16, 95% CI: 1.18 to 14.70; PTSD: 14.41, 95% CI: 3.91 to 53.13). The prevalence of depression was higher among repeat compared with single flooded participants, but this was not significant after adjustment. There was no difference in levels of anxiety or PTSD. Compared with unaffected participants, those flooded had lower EQ-5D-5L index scores (adjusted coefficient: −0.06, 95% CI: −0.12 to −0.01) and lower self-rated health scores (adjusted coefficient: −6.99, 95% CI: −11.96 to −2.02). There was, however, little difference in HRQoL overall between repeat and single flooded participants. Conclusions Interventions are needed to help minimise the impact of flooding on people’s mental health and HRQoL.