Serum IgE levels and the expression of low affinity receptor for IgE (FcεRII/CD23) are increased in cutaneous leishmaniasis. The ligation of CD23 receptor by IgE–anti-IgE immune complexes results in nitric oxide (NO) production, which is a critical leishmanicidal factor. Human monocytes/macrophages express FcεRII/CD23 after activation with IFN-γ and IL-4. In the present study, we assessed the relationship between NO, total and Leishmania-specific IgE and soluble CD23 across the clinical spectrum of American cutaneous leishmaniasis (ACL). Sixty-nine ACL patients and 22 endemic controls were studied. NO concentration was estimated using the Greiss method. Soluble CD23, total IgE and anti- Leishmania IgE levels were measured using ELISA. Soluble CD23 was increased in the four patient groups (0.001< P<0.05) compared by the Mann–Whitney test to healthy subjects, particularly in mucocutaneous leishmaniasis (MCL) and diffuse cutaneous leishmaniasis (DCL) patients. Total IgE levels were higher in ACL patients ( P<0.0001). Anti- Leishmania IgE showed a similar tendency, where MCL and DCL patients had greater levels. All patients groups, except intermediate or chronic cutaneous leishmaniasis (ICL) patients, showed elevated levels of NO 2 −/NO 3 − compared to healthy individuals (0.001< P<0.01). Interestingly, ICL patients did not produce significant levels of NO 2 −/NO 3 −. ACL patients showed a significant positive correlation between soluble CD23 and anti- Leishmania IgE. DCL patients showed a positive correlation between both parameters. Overall results suggest that sCD23, IgE and NO may play different roles across the ACL spectrum.