Technical advances including liquid chromatography-tandem mass spectrometry and its data analysis enable detailed proteomic analysis of the nasal mucus. Alterations of the nasal mucus proteome may provoke substantial changes of the nasal physiology and have already been associated with rhinologic diseases such as allergic rhinitis. This study was conducted as a pilot study to map the olfactory cleft proteome using current techniques for proteomic analysis. Furthermore, we aimed to investigate proteomic changes as potential biomarkers in patients suffering from idiopathic and postinfectious olfactory disorders compared to healthy controls. Seven patients with idiopathic hyposmia and anosmia, seven patients with postinfectious hyposmia and anosmia and seven healthy controls were included in this study. In total, 1117 different proteins were detected in at least five patients in at least one group. Results of this study did not reveal significant differences regarding the proteomic composition of the olfactory cleft mucus between patients versus healthy controls. Among proteins involved in olfactory perception the G protein family was detected but also found unchanged between groups. Investigation of protein composition by liquid chromatography-tandem mass spectrometry enabled us to perform an in-depth analysis of the olfactory cleft mucus proteome regarding the diversity of different proteins in individual patients. However untargeted proteomics of the olfactory cleft mucus may not be an applicable approach to develop biomarkers for olfactory disorders. Targeted analyses of distinct proteins known to be involved in olfactory perception but not detected by our approach, e.g. odorant binding proteins, may provide more information regarding pathophysiology of olfactory diseases.