BACKGROUND: Intravenous artesunate has replaced quinine as the first-line therapy for severe imported malaria, given its anti-malarial superiority shown in clinical trials conducted in endemic countries. Evidence for red blood cell (RBC) exchange in patients with severe malaria treated with artesunate is lacking. This retrospective cohort study describes the experience at Hospital Clinic of Barcelona with the use of artesunate for severe malaria and the joint use of RBC exchange in selected cases. METHODS: Patients treated for severe malaria at Hospital Clinic of Barcelona between August 2013 and January 2015 were included in this retrospective study. Severe malaria was defined according to WHO criteria. Data were extracted from electronic hospital records. A log-linear mixed model approach was used to estimate parasite clearance times. RESULTS: Within the study period, 42 patients were diagnosed of malaria at this centre, of which 38 had Plasmodium falciparum (90.5 %). Sixteen patients (42 %) had severe malaria cases and were treated with intravenous artesunate. Four patients underwent RBC exchange within a period of 15 h after the first dose of artesunate (range 9-21 h). The procedure lasted a median of 2 h (IQR 1.8-2 h), using a median of 12 (IQR 11-14) units of packed RBCs to replace a median of 3794 ml (IQR 2977-4343). The technique was well-tolerated without haemodynamic complications. There were no deaths. The regression model showed an estimated time to 95 % decay of 21.6 h (95 % CI 17.3-28.8). When assessing effect modification by RBC exchange, there was no difference in the parasite elimination rate (p = 0.286). DISCUSSION AND CONCLUSION: In this study RBC exchange failed to show benefits in terms of parasite clearance probably due to the small number of patients analysed. The evidence for exchange transfusion remains limited.