Background: We assessed the mental health of individuals in the general population, during an initial period of easing of COVID-19 restrictions in the Republic of Ireland (RoI). Methods: Data were collected through a nationally representative cross-sectional telephone survey, during the first period of easing of restrictions during the COVID-19 pandemic between May and July 2020. Mental health was examined using the Patient Health Questionnaire Anxiety Depression Scale. Poisson regression analyses were conducted to estimate risk ratios with robust variance estimation of the association between selected demographic factors and the risk of having depression and anxiety symptoms. Results: Of the 1,983 participants, 27.7% (n = 549; 95% CI: 0.26 - 0.30) reported depression and anxiety symptoms, while 74 (3.8%; 95% CI: 0.03 - 0.05) disclosed self-harm and/or suicidal thoughts. Females (RR: 1.60, 95% CI: 1.37 - 1.87, p < 0.0005), employed individuals who experienced a change in work status (RR: 1.50, 95% CI: 1.24 - 1.82, p < 0.0005), participants cocooning due to a health condition (RR: 1.34, 95% CI: 1.08 - 1.66, p< 0.01), participants who were self-isolating (RR: 1.25, 95% CI: 1.03 - 1.51, p=0.025) and moderate-heavy drinkers (RR: 1.27, 95% CI: 1.09 - 1.47, p<0.01) were at increased risk of depression and anxiety. Young people aged 18-29 years and those in the two lowest income categories were most likely to report self-harm and/or suicidal thoughts. Conclusion: As the COVID-19 pandemic continues, with further waves and associated restrictions, the impact on mental health in the population as a whole and in specific subgroups must be considered. Study protocol registration: doi.org/10.12688/hrbopenres.13103.2.