The Post-COVID Syndrome (PCS) currently affects approximately 3-17% of people after infection with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has the potential to become a significant global health burden. The Post-COVID Syndrome has various symptoms, and currently, methods for improved PCS scoring are developed to guide therapy. Yet mechanistic insights and treatment options are scarce. We thought to investigate individual nasal epithelial cells from patients with various levels of PCS intensity to gain mechanistic insights. We performed single-cell RNA sequencing (Signleron, Germany) from nasal biopsies samples (n=30) of clinically well-characterized patients with mild, moderate or severe PCS symptoms based on a recently published PCS score (Bahmer et al). Transcriptional profiles of 35.000 cells identified 18 different cell types, such as all major epithelial cell types of the conducting airways, including basal, secretory, and ciliated cells. In addition, we used enrichment analysis to link key molecules and biological pathways to disease severity. High PCS scores are associated with decreased levels of ciliated cells and an increase in the total number of immune cells. Significantly associated signaling pathways included NFkB and WNT signalling, and signal-response Reactome interactions between immune cells and epithelial cells were detected. An immune/epithelial cross-talk may decrease ciliated epithelial cells, which might interfere with a proper mucosal barrier function. These findings could be further investigated as a therapeutic option for preventing severe outcomes in symptomatic post-Covid patients.