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Cellular immunity after SARS-CoV-2 infection or immunization may be important for long-lasting protection against severe COVID-19 disease. We investigated cellular immune responses after SARS-CoV-2 infection and/or vaccination with an interferon (IFN)-γ release assay (QuantiFERON, QFN). In parallel, we measured SARS-CoV-2 anti-Nucleocapsid (Abs-N), anti-Spike (Abs-S) and Neutralizing (NAbs) antibodies against SARS-CoV-2 wild type and Omicron variant. We recruited 41 participants: unvaccinated children and adults and vaccinated uninfected or vaccinated convalescent adults. All vaccinated adults had received three doses of the BNT162b2 COVID-19 vaccine at 6.2–10.9 months prior to their inclusion to the study. All the unvaccinated participants were tested negative with QFN. Regarding the vaccinated population, 50% (8/16) of the vaccinated uninfected adults and 57.1% (8/14) of the vaccinated convalescent adults were tested positive. Among the QFN positive individuals, a reactive response to antigen (Ag) 1 (CD4+ epitopes) and to Ag2 (CD4+ and CD8+ epitopes), was detected in 68.8% (11/16) and 87.5% (14/16) respectively, while 56.3% (9/16) had a reactive response to both antigens. Additionally, Ag1 IFN-γ values correlated with Abs-S (P P = 0.039) levels, but not with NAbs against Omicron variant (P = 0.09) and Ag2 IFN-γ values correlated only with Abs-S levels (P = 0.009). The SARS-CoV-2 QFN assay did not detect T cellular responses in unvaccinated individuals and in a significant number of vaccinated individuals. Further comparative studies with different immunology assays are required to elucidate whether this is the result of waning immunity or low sensitivity of the assay.