Objective To perform an epidemiological investigation on a case of visceral leishmaniasis reported from Shule County, Kashi Prefecture, Xinjiang Uygur Autonomous Region in 2021, so as to provide insights into differential diagnosis of visceral leishmaniasis during the COVID-19 pandemic. Methods The epidemiological history of this case was collected, and the case was diagnosed for Leishmania infection with the immunochromatographic (rK39) strip test, bone marrow smear microscopy and PCR assay. Results The patient had typical clinical symptoms of leishmaniasis, including irregular fever, hepatosplenomeg- aly, low serum albumin and elevated globulin. Bone marrow smear microscopy identified L. donovani amastigotes, and both rK39 strip test and PCR assay were positive, while the case was tested negative for SARS-CoV-2. COVID-19 was therefore excluded and visceral leishmaniasis was diagnosed. Standard full-dose treatment with sodium stibogluconate was given, and no Leishmania was found on blood smears during the reexamination. No recurrence was found during the followup after discharge for hospital. Conclusions During the COVID-19 pandemic, it is recommended to increase the perception of differential diagnosis of visceral leishmaniasis among first-contact doctors, and reinforce the capability of differential diagnosis and health education of visceral leishmaniasis among medical and healthcare institutions at all levels, to prevent missed diagnosis and misdiagnosis of visceral leishmaniasis.