OBJECTIVES: The emergence of a new mpox sub-clade Ib and changes in transmission pattern are of concern. To inform strategies to protect populations and improve outcomes, we implemented a rapid research needs appraisal (RRNA) to identify existing evidence on mpox clade I. METHODS: We searched Embase, MEDLINE, Scopus, and grey literature to 11 February 2025 for human mpox clade I studies. RESULTS: Of 79 studies identified, 2.5% (2/79) were interventional, 97.4% (77/79) observational, presenting data on 59,183 mpox cases. Most (57/79) focused on clade Ia, 16/79 clade Ib, and 6/79 unspecified sub-clade I. 90.8% were set in Africa. Studies focused on clinical characteristics (n = 55), transmission (n = 23), risk factors for disease/severe disease (n = 13), diagnostics (n = 9), social/behavioural factors (n = 6), immune response/seroprevalence (n = 5), and vaccine/treatments (n = 4). Symptoms and complications were similar for both sub-clades. Three studies reported foetal death in 8/12-8/14 pregnant women infected with clade Ib and in 3/4 of women with clade Ia. The pooled case fatality rate (CFR) was 6% (95% CI 3% to 8%) in clade Ia studies and 1% (95% CI 0% to 1%) in clade Ib studies. There were no studies on effectiveness of prevention, treatment, risk of asymptomatic infection, or immune protection over time. CONCLUSION: The identified evidence-gaps provide a baseline to inform coordinated research strategies to generate evidence for clinical and public health responses to improve outcomes.