Abstract Objective To determine whether prepandemic sera from patients with Chagas disease recognise SARS‐CoV‐2 antigens. Materials and Methods Forty sera from patients with Chagas disease were tested for the presence of IgG cross‐reactivity against the nucleocapsid protein (NP) and spike (S) SARS‐CoV‐2 proteins by ELISA. Positive samples were tested again using a different ELISA and CLIA, both against NP. Results None of the sera from patients with Chagas disease, previously confirmed as positive for the presence of anti‐ Trypanosoma cruzi antibodies reacted against the SARS‐CoV‐2 S protein, and six samples tested positive for the NP antigen (15%). The six positive samples were re‐tested, five remained positive by ELISA and all were negative by CLIA. Conclusion According to our data, false‐positive results might be a concern in the detection of SARS‐CoV‐2 antibodies in patients with Chagas disease.