Summary Sickle cell disease (SCD) is characterised by chronic haemolysis and oxidative stress. Herein, we investigated 30 SCD patients and found 40% with elevated mitochondria levels (SS‐mito+) in their mature red blood cells, while 60% exhibit similar mitochondria levels compared to the AA group (SS‐mito−). The SS‐mito+ patients are characterised by higher reticulocytosis and total bilirubin levels, lower foetal haemoglobin, and non‐functional mitochondria. Interestingly, we demonstrated decreased levels of mitophagy inducers, PINK1 and NIX, and higher levels of HSP90 chaperone in their red cells. Our results highlighted for the first time an abnormal retention of mitochondria in SCD linked with mitophagy‐related proteins.