Background: Pemphigus Vulgaris (PV) is a severe autoimmune blistering disease which may affect the patient's health‐related quality of life (HR‐QoL) and mood even during quiescent disease activity. We sought to evaluate HR‐QoL, quality of sleep (QoS), anxiety and depression in oropharyngeal PV patients (OPV) in complete clinical remission on or off therapy (CCR‐on, CCR‐off). Methods: Thirty OPV patients and 30 healthy controls were enrolled. The Short Form 36 Health Survey Questionnaire (SF‐36), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM‐D) and Hamilton Rating Scale for Anxiety (HAM‐A) were administered. Descriptive statistics, including the Mann‐Whitney U test and hierarchical multiple linear regression analysis, were used. Results: The OPV patients had statistically lower scores in the majority of items of the SF‐36 and higher scores in the PSQI, HAM‐A and HAM‐D than the healthy controls (P <.004; P <.001; and P <.001 respectively). Nine (30%) of the OPV patients were poor sleepers (PSQI > 5) with higher scores in the SF‐36, HAM‐A and HAM‐D compared with the good sleepers (PSQI < 5). No statistically significant difference was detected in the OPV group when comparing patients in CCR‐on and CCR‐off, or in consideration of the cumulative time of the disease duration. Conclusions: HR‐QoL of OPV patients can be impaired even over periods of relatively well‐being, therefore, clinicians should monitor periodically their HR‐QoL, QoS and psychological profile in order to guide treatments also toward improving their HR‐QoL. [ABSTRACT FROM AUTHOR]