Background: We aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with tissue-borne parasitic infections. Methods: We tested three SARS-CoV-2 antibody-detection assays [cPass SARS-CoV-2 Neutralization Antibody Detection Kit (cPass), Abbott SARS-CoV-2 IgG assay (Abbott Architect), and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test ("SD RDT IgM"/"SD RDT IgG")] among 559 pre-COVID-19 seropositive sera for several parasitic infections. Results: The specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥ 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay. Conclusions: The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.