Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n= 7) and normosmic (n= 4) patients. Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted Pvalue considered statistically significant (P< 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P< 0.05, FDR correction) including IL‐4 and IL‐13 signaling, IL‐10 signaling, and rhodopsin‐like receptors. RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL‐10, rhodopsin‐like receptors, and IER3in the pathogenesis of olfactory dysfunction. What are the significant findings of the study? Differential gene expression between normosmic and dysosmic chronic rhinosinusitis without nasal polyps (CRSsNP) patients showed upregulation of Immediate Early Response 3 (IER3).Reactome analysis showed that IL‐10 signaling, IL‐4/IL‐13 signaling, rhodopsin‐like receptors, and binding of chemokines to chemokine receptors were different between dysosmics and normosmics. Differential gene expression between normosmic and dysosmic chronic rhinosinusitis without nasal polyps (CRSsNP) patients showed upregulation of Immediate Early Response 3 (IER3). Reactome analysis showed that IL‐10 signaling, IL‐4/IL‐13 signaling, rhodopsin‐like receptors, and binding of chemokines to chemokine receptors were different between dysosmics and normosmics. What does the study add? This is the first study to utilize RNA sequencing of superior turbinate mucosa to investigate olfactory dysfunction in CRSsNP patients.The study highlights potential areas of future investigation including IL‐10 signaling, rhodopsin‐like receptors, and IER3. This is the first study to utilize RNA sequencing of superior turbinate mucosa to investigate olfactory dysfunction in CRSsNP patients. The study highlights potential areas of future investigation including IL‐10 signaling, rhodopsin‐like receptors, and IER3.