Background/Objectives: Chronic pain (CP) is a public health problem with significant consequences for the patient’s life. This study aims to analyze the prevalence of sick leave due to CP in Spain and to explore how pain intensity and mental disorders mediate the relationship between sick leave and health-related quality of life (HRQL) in subjects with CP.

Methods: A cross-sectional study was conducted with 7,058 participants, representing the Spanish adult population. Sociodemographic information, presence and characteristics of CP, sick leave due to CP, anxiety and depression (HADS) and HRQL (SF-12v2) were collected. The prevalence of sick leave and four serial multiple mediation analyses were calculated.

Results: CP prevalence was 25.9% (95%CI: 24.8-26.9), while 28.6% (95%CI: 26.4-30.8) needed sick leave due to CP in the last year. Sick leave was associated with worse HRQL through the mediating effect of pain intensity and anxiety/depression, showing a total mediation for mental component summary of the SF-12v2. Serial mediation analyses showed that CP sick leave was associated with poorer physical and mental HRQL, largely explained by pain intensity and anxiety/depression after controlling for age and sex. The strongest effects were indirect, particularly the serial pathways linking pain intensity to emotional symptoms, highlighting their central role in HRQL impairment.

Conclusions/Recommendations: This study highlights the strong impact of CP on the Spanish workforce, providing new insights into the mechanism by which CP sick leave may hinder HRQL through the mediation effect of pain intensity and mental disorders.

Funding: Foundation for the management of Biomedical Research of Cádiz (FCÁDIZ) and the Grünenthal Foundation.