We performed Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS) on primary patient olfactory neuroepithelial derived cells (ONS) from both idiopathic PD (iPD) and healthy controls and identified 228 differentially quantified proteins. Reactome pathway analysis revealed that the “Neutrophil degranulation and XBP1(S) activates chaperone genes pathways” were the most affected, indicating disruption of the secretory pathway. Upon closer inspection we identified that proteins associated with the endoplasmic reticulum and the secretory pathways were the most abundantly changed, in particular proteins associated with the unfolded protein response (UPR). In order to validate this finding, we performed qRT-PCR analysis on patient ONS subjected to ER stressors and confirmed that the iPD patient cells had elevated UPR responses, in particular to tunicamycin mediated ER stress.