Background: 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 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, 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 (ssGESA), Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource, 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 cells (P = 0.039) and Th2 cells (P = 0.016), and it had fewer Th17 cells (P = 0.008), Tgd (P < 0.001) and NK CD56dim cells (P = 0.047). The differences between the left and right atrium in AF and SR were analyzed. In AF atrium tissue, a total of 88 DGEs (26 up-regulated, 61 down-regulated) were obtained. The enrichment signaling pathways and biological functions of DGEs were predicted. Conclusions: The differing immune infiltrating cells and DEGs in left and right atrium indicate that there are different mechanisms for development remodeling and inflammatory environment of AF within the left and right atrium.