Background Cardiac involvement is the most common complication of Kawasaki disease (KD); however, the underlying mechanisms are not understood. The present study was designed to investigate changes in plasma hydrogen sulfide (H 2S) and nitric oxide (NO) levels in the acute and recovery stages of KD children and to examine their clinical significance. Methods Thirty-five KD patients and 32 healthy children were enrolled in the study. KD patients were divided into two subgroups: a non-cardiac involvement group and a cardiac involvement group. Plasma H 2S levels were measured using the sulfur-sensitive electrode method and plasma NO levels and NO synthase activity were determined using the nitrate reductase method both before and after intravenous immune globulin (IVIG) therapy. Results Plasma H 2S levels significantly decreased in KD patients during the acute phase of the disease and NO levels were significantly increased, compared with the control group (P <0.01). After treatment with IVIG, both plasma H 2S and NO levels significantly increased (P <0.01). The plasma levels of H 2S were significantly lower in the cardiac involvement group compared with the non-cardiac involvement group (P <0.05). Conclusion H 2S and NO may play a role in the pathophysiological process of inflammation during the acute phase of KD. Endogenous H 2S may exert protective effects with respect to cardiac complications in KD.