The apoptotic molecule Fas and its ligand FasL are involved in the process of T-lymphocyte death, which may lead to lymphopenia, a characteristic of severe coronavirus disease 2019 (COVID-19). In this study, we investigated the influence of polymorphisms in the FAS and FASL genes, FAS and FASL gene expression, and plasma cytokine levels on COVID-19 severity and long COVID occurrence. A total of 116 individuals with severe COVID-19 and 254 with the non-severe form of the disease were evaluated. In the post-COVID-19 period, samples from 196 individuals with long COVID and 67 from people who did not have long COVID were included. Genotyping and quantification of gene expression were performed via real-time PCR, and cytokine measurement was performed via flow cytometry. The AA genotype for FAS rs1800682 (A/G) and the TT genotype for FASL rs763110 (C/T) were associated with increased FAS and FASL gene expression, respectively (p < 0.005). Higher plasma IFN-γ levels were associated with higher FAS and FASL gene expression (p < 0.05). Among individuals with non-severe COVID-19, carriers of the AA genotype for FAS rs1800682 (A/G) had higher levels of FAS expression, more symptoms, and higher IFN-γ levels (p < 0.05). No association of the evaluated markers with long COVID were observed. The AA genotype of FAS rs1800682 (A/G) and the TT genotype of FASL rs763110 (C/T) influence the levels of FAS and FASL gene expression. Higher gene expression of FAS and FASL may lead to greater inflammation in COVID-19 patients, with higher levels of IFN-γ and T lymphocyte death.