Purpose <p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition associated with functional impairment and a relevant socioeconomic burden. While direct healthcare costs have been partially described in Spain, indirect costs related to loss of work productivity remain insufficiently characterized. This study aimed to estimate the indirect costs associated with CRSwNP in Spain from a societal perspective, focusing on productivity losses due to absenteeism and presenteeism.</p> Methods <p>A cost-of-illness analysis with a one-year time horizon and a societal perspective was conducted in working-age adults (18–64 years) with CRSwNP in Spain. Disease prevalence (0.8%) was derived from national epidemiological studies. Productivity loss was estimated using published data on absenteeism and presenteeism, assuming a mean of 49.8 equivalent lost productivity days per patient per year. Economic valuation followed the human capital approach, applying average total labor costs and adjusting for labor market participation. Deterministic sensitivity analyses explored parameter uncertainty.</p> Results <p>An estimated 242,582 working-age adults were affected by CRSwNP, of whom 169,808 were effectively employed. The mean annual indirect cost per employed patient was €8,178.65, with presenteeism accounting for 60% and absenteeism for 40%. Extrapolation to the national level resulted in an estimated annual productivity loss of €1.39 billion, ranging from approximately €0.9 billion to nearly €2.0 billion in sensitivity analyses.</p> Conclusions <p>CRSwNP is associated with substantial productivity losses in Spain, leading to a considerable indirect economic burden predominantly driven by presenteeism. These findings support the inclusion of indirect costs in assessments of disease burden and healthcare decision-making.</p>