The optimal management of immunosuppression in transplant patients infected with COVID‐19 is unknown. We performed an in vitro study to determine the effect of individual immunosuppressive agents on SARS‐CoV‐2‐specific T‐cell cytokine expression. Convalescent peripheral blood mononuclear cells from eleven non‐immunosuppressed patients with COVID‐19 were preincubated with clinically relevant concentrations of immunosuppressive drugs (tacrolimus, mycophenolate, sirolimus, prednisone) and then stimulated with a SARS‐CoV‐2 peptide pool. Supernatants were analyzed by 14‐plex high sensitivity T‐cell cytokine array. With increasing concentrations of tacrolimus, there was a trend to reduction in the release of IL‐2 (p = .0137), and IFN‐γ (p = .0147) in response to peptide stimulation. There was also a subsequent trend toward a Th2 phenotype, indicated by lower IFN‐γ:IL‐13 ratio (p = .0663) and IFNγ:IL‐4 ratio (p = .0176). Sirolimus appeared to be associated with a proinflammatory cytokine release, including TNF‐α (p = .0027) and IL‐1β (p = .0016), in response to SARS‐CoV‐2 peptides. In contrast, mycophenolate and prednisone did not influence the SARS‐CoV‐2‐specific cytokine response. These are preliminary findings only, with larger studies required to inform clinical recommendations.