Background: HLA‑G, a non‑classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting mater‑ nal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA‑G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA‑G and malaria, latent class analysis was used to test whether distinct sub‑populations of children, each with distinctive soluble HLA‑G evolutions may suggest the existence of groups presenting variable malaria susceptibility. Method: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA‑G was studied by the latent class method. Results: Three groups of children were identified: one with consistently low levels of soluble HLA‑G during follow‑up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA‑G. Placental malaria was not. Presence of soluble HLA‑G in cord blood increased the probability of belonging to the highest trajectory. Conclusion: These results, together with previous ones, confirm the important role of HLA‑G in the individual sus‑ ceptibility to malaria. Assaying soluble HLA‑G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood.