The COVID-19 pandemic imposed additional and specific challenges on the lives and wellbeing of informal unpaid carers. Addressing an important gap in the existing literature, this systematic review (prospectively registered with PROSPERO CRD42022376012) synthesises and evaluates the quantitative evidence examining the association between unpaid caregiving and mental health (compared to non-caring), during the pandemic. Five databases were searched (Medline, PsycInfo, EMBASE, Scopus, Web of Science) from Jan 1, 2020, to March 1, 2023. Population-based, peer-reviewed quantitative studies using any observational design were included, with screening, data extraction and quality assessment (amended NOS) independently conducted by two reviewers. Of the 3,073 records screened, 20 eligible studies (113,151 participants) were included. Overall quality of evidence was moderate. Narrative synthesis was complemented by Effect-direction and Albatross plots (given significant between-study heterogeneity precluded meta-analysis). Results indicate that the mental health of informal carers, already poorer pre-COVID compared to non-caregivers, was disproportionally impacted as a result of the pandemic and its associated public health containment measures. This review highlights the vulnerability of this group and should motivate political will and commensurate policies to ensure unpaid caregivers are better supported now, in the medium term, and crucially if, and when, another global public health emergency emerges.