The overall incidence of asthma in children with sickle cell disease in French Guiana is unknown. Asthma is common in children with sickle cell disease and is associated with increased morbidity and mortality. This study aimed to describe the impact of asthma on the occurrence of acute chest syndrome in children with sickle cell disease who were followed up in French Guiana. We performed a multicenter nested case-control study between January 2012 and December 2022. Our study population consisted of children, aged between 6 months and 18 years, who were diagnosed with sickle cell disease at birth and hospitalized at least once for acute chest syndrome during the study period. A total of 588 children were followed up for sickle cell disease. Of these, 390 had sickle cell disease, 180 had SC, and 18 had Sβ + thalassemia. Of the 390-sickle cell disease, we identified 35 who also had asthma, giving an estimated prevalence of asthma of 8.9% among children with sickle cell disease in French Guiana. Only asthma was significantly associated with acute chest syndrome ( < 0.001). The prevalence of asthma in children with sickle cell disease is underestimated. Asthma is an independent risk factor for acute chest syndrome. Given the seriousness of asthma in children with sickle cell disease, systematic screening for asthma in children with sickle cell disease has been implemented. This screening, which will be evaluated after one year, will help to better characterize asthmatic children with sickle cell disease and improve their care.