Dysfunctions in the immune system and alterations in the microbiome composition following SARS-CoV-2 infection contribute to persistent neurological issues observed in long COVID-19 survivors. We hypothesize that alterations in the gut microbiome composition and peripheral inflammatory profile following COVID-19 may play pivotal roles in behavior changes among individuals experiencing long-term illness. This cross-sectional study included a sample of post-COVID-19 and non-COVID-19 subjects. We assessed the presence of psychiatric conditions utilizing standardized diagnostic criteria, Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression (HAM-D), Biological Rhythms in Neuropsychiatry Assessment Interview (BRIAN), and Functional Assessment Short Test (FAST). Plasma samples were analyzed to examine lipid and inflammatory profiles. Fecal samples were evaluated by 16S rRNA sequencing to identify the gut microbiome composition. Noteworthy findings include a significant increase in the myeloid progenitor inhibitory factor 1 (MPIF-1), interleukin (IL)-17, and triglyceride among post-COVID-19 individuals. While α-diversity in the gut microbiome composition showed no significant differences, β-diversity demonstrated a notable distinction between the healthy control and post-COVID-19 groups. Post-COVID-19 individuals exhibited a decreased abundance of phylum, class, and order of Verrucomicrobia, family, and genus of Akkermansia, a short-chain fatty acid producer and microbial group significantly associated with intestinal barrier homeostasis and the amelioration of metabolic diseases. No difference was found between the behavioral and clinical data. In post-COVID-19 individuals, there were elevated IL-17 and MPIF-1 levels, compared to non-COVID-19 individuals. Additionally, there were notable alterations in gut microbiome composition, as evidenced by changes in β-diversity and a decrease of Verrucomicrobia, family, and Akkermansia genus abundance.