Reports on dengue morbidity in patients with sickle cell disease (SCD) are scarce. Dengue is arthropod-borne viroses due to dengue virus (DENV) and affects populations with a high prevalence of SCD; therefore, the risk of morbidity may be increased. To determine the impact of dengue infection in SCD patients, we reviewed medical records during a vast outbreak of dengue virus serotype-2 (DENV-2) in French Guiana in 2012-2013. We identified 10 cases of laboratory-confirmed dengue infection; these were classified into A, B and C categories based on levels of severity of dengue according to World Health Organisation (WHO). The average age of SCD patients was 18.2 years. 1, 6 and 3 cases were classified as A, B and C WHO severity criteria, respectively. All patients had an important decrease in haematocrit (while one of the WHO severity criteria is the increase of haematocrit). Only one patient had decreased platelet count. Seven cases had vaso-occlusive crisis (VOC), six patients developed acute hepatitis and eight had a simultaneous bacterial infection. Six of them needed a blood transfusion. The results suggested that the WHO severity laboratory criteria of hemoconcentration and platelet counts were not helpful in the management of SCD patients. The morbidity was mainly caused by specific complications of SCD, especially VOC, likely facilitated by vascular endothelial damages consecutive to dengue fever, severe haemolysis, hepatitis and bacterial co-infections.