Summary Procalcitonin (PCT) plasma levels and the fraction of CTLA‐4‐positive T cells are both elevated in acute Plasmodium falciparum malaria in human adults and the degree of elevation is positively correlated with other markers of disease severity, for example with parasitaemia. However, the clinical manifestations of malaria are strongly age‐dependent and children from endemic areas carry the main disease burden. Therefore, we measured PCT plasma levels and CTLA‐4 expression by T cells in four groups of children from the Ashanti Region in Ghana: asymptomatic children with or without parasitaemia, children with uncomplicated P. falciparum malaria and children with severe disease. PCT levels were highly elevated in both groups with acute malaria but they did not discriminate between uncomplicated and severe disease. In contrast, CTLA‐4‐expression by T cells was increased only in severe malaria. The fraction of CTLA‐4 positive T cells in the blood of children with severe disease differed significantly from that in uncomplicated malaria, which was not elevated in spite of the high parasite loads observed in these children. This was unexpected, as in adults uncomplicated malaria is associated with a dramatic sixfold increase of the fraction of CTLA‐4‐positive T cells. The data from this study support the hypothesis that strong T cell activation as measured here by CTLA‐4 expression is not just the by‐product of a high parasite burden, but that it contributes to the pathogenesis of P. falciparum malaria.