Background Early biomarkers of the response to treatment are lacking and may help to reduce mortality by the vector‐borne disease visceral leishmaniasis (VL). Methods A prospective cohort study was conducted to investigate plasma cytokines and clinical laboratory data as biomarkers of the early response to specific treatment for VL in 36 patients. Results The mean interleukin 6 (IL‐6) concentration on the 7th day was 2.3% of the pre‐treatment concentration, interleukin 10 (IL‐10) was 8.0%, and interleukin 8 (IL‐8) was 8.2%. On the 7th day, IL‐10 was below half of the pre‐treatment concentration in 100.0%, IL‐8 in 95.5% and IL‐6 in 90.9%. The spleen and liver sizes, haemoglobin, interleukin 1 beta (IL‐1β) and tumour necrosis factor alpha (TNF‐α) showed a slower recovery. Fever disappeared in 91% on the 7th day, 69.4% had a normal white cell count, and 77.8% had a normal platelet value by this time. Conclusions The plasma cytokines IL‐6, IL‐10 and IL‐8 were demonstrated to be excellent markers of the early response to VL treatment and if tested before the 7th day, will likely prove to be better than fever measurement.