O’nyong-nyong virus (ONNV) is an alphavirus transmitted by main malaria vectors (Anopheles spp.) suggesting the possibility of co-infections in endemic areas. However, the potential pathological outcomes of such interactions in humans remain unknown. Using murine malaria models, we investigated the effects of pre-existing Plasmodium infections in the development of ONNV-associated pathologies. We report that Plasmodium infections suppressed hallmark ONNV-induced footpad swelling and viremia. In-vivo monitoring of ONNV replication kinetics in infected footpads revealed reduced viral load during the first 24 hours post-virus infection. Flow cytometry analysis showed that pre-existing Plasmodium infections rendered footpad CD45+ cells (monocytes/macrophages) and CD45- cells (fibroblasts, myoblasts and endothelial cells) less susceptible to ONNV. Quantification of immune soluble factors in serum and footpad tissue lysates of Plasmodium-infected mice yielded increased levels of antiviral interferon gamma (IFNγ) which prompted further assessment of its role in the suppression of ONNV replication. Antibody blockade of Plasmodium-induced interferon-γ or co-infection in IFNγ-deficient animals restored ONNV replication to similar levels than animals singly-infected by ONNV. These results suggest that Plasmodium-induced interferon-γ restricts ONNV replication in mice.