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Abstract Background Africa continues to have a significant public health problem with mpox, where endemic transmission persists and overlaps with a high burden of other infectious diseases. Although their epidemiology and clinical impact are still poorly understood throughout the continent, coinfections with human immunodeficiency virus (HIV) and varicella-zoster virus (VZV) can affect the clinical picture, severity of the disease, and accuracy of the diagnosis. Methods Following PRISMA criteria, we registered the protocol in PROSPERO (CRD420251133960) and carried out a methodical review and meta-analysis. Through searches of numerous electronic databases and grey literature up to February 27, 2025, observational studies documenting mpox coinfections with VZV and/or HIV and related clinical symptoms in Africa were searched. Pooled prevalence was calculated using random-effects models. Subgroup analyses and meta-regression were conducted to investigate heterogeneity across WHO regions, countries, study designs, settings and type of participants. Results A total of 27 studies carried out across African countries were included. The pooled prevalence of VZV–mpox coinfection was 10.23% (95% CI: 2.95–29.93), while HIV–mpox coinfection prevalence was 6.55% (95% CI: 2.36–16.90), both of which had significant heterogeneity. Coinfections were far more prevalent in hospital-based environments than in community-based research. The rash was nearly universal throughout all clades, but the clinical manifestations varied depending on the viral clade, with clades I and Ia linked to more severe systemic symptoms than clade II. Discussions HIV and VZV coinfections with mpox pose a major yet possibly underestimated burden in Africa and are linked to more severe clinical presentations, particularly in hospital environments. The necessity of including clinical, epidemiological, and genomic data into mpox monitoring systems is emphasized by the observed clinical differences between clades. Improving patient management and outbreak preparedness across the continent requires strengthening diagnostic capacity and routinely screening for coinfections.