Background: Information on the difference between left and right atrium in Atrial fibrillation (AF) is still lacking. In the present study, we aimed to identify differences in immune cell infiltration and differentially expressed genes (DEGs) between atrial tissue in patients with AF and sinus rhythm (SR), and to compare the differences between left and right atrial tissues in AF. Methods: The gene data of GSE79768 (Gene Expression Omnibus Series79768) , GSE115574, and GSE128188 from the Gene Expression Omnibus (GEO) database were retrieved. After merging all data and adjusting batch effect, DEGs were identified. Single-Sample Gene Set Enrichment Analysis (ssGSEA), Functional enrichment analysis based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, and ESTIMATE algorithm were carried out to analyze the difference between AF and SR. Results: In total, 105 atrial samples from 3 studies were included in the analysis. Compared with SR, AF tissue had more CD8+ T (cluster of differentiation 8+ T) cells (p = 0.039) and Th2 (T helper 2) cells (p = 0.016), and it had fewer Th17 cells (p = 0.008), Tgd (p < 0.001) and NK (natural killer) CD56dim cells (p = 0.047). The differences between the left and right atrium in AF and SR were also analyzed. In AF atrium tissue, a total of 87 DEGs (26 up-regulated, 61 down-regulated) were identified. The enrichment signaling pathways and biological functions of DEGs were predicted. Conclusions: The difference in infiltrating immune cells and DEGs between left and right atrium indicates that there are different mechanisms for development remodeling and inflammatory environment of AF within the left and right atrium.