Objective <p>Indolent non-Hodgkin lymphoma (iNHL) is a chronic, incurable lymphoid malignancy with a slow course. In absence of symptoms, a ‘watchful waiting’ approach is often chosen. The emotional burden of uncertainty and monitoring may affect patients’ psychological well-being. This study investigates the extent of psychological distress in iNHL patients and its relationship with sociodemographics, clinical characteristics, and quality of life.</p> Methods <p>A cross-sectional study was conducted among adults with histologically confirmed indolent B-cell or T-cell NHL, recruited via a regional Dutch hospital and the online patient platform CMyLife. Data were collected through self-administered online questionnaires, including sociodemographics, clinical characteristics, psychological distress (HADS) and quality of life (EORTC QLQ-C30/LG-NHL).</p> Results <p>A total of 352 iNHL patients completed the questionnaires (response rate: 37.5%). The mean age was 69&#xa0;years, 58.5% were male and psychological distress (HADS ≥ 13) was observed in 30.7% of participants. Distressed patients were more often female, less educated, more frequently in the period of watchful waiting, and had more medical comorbidities (p &lt; .01). They reported significantly lower health-related quality of life (HRQoL) (mean 51.2 vs. 77.6) and a higher symptom burden. Psychological distress was strongly correlated with lower HRQoL (r = –.63). In hierarchical regression analysis, psychological distress was the strongest predictor of lower HRQoL (β = –0.605, p &lt; .001).</p> Conclusions <p>Approximately one-third of iNHL patients experience psychological distress, significantly associated with female gender, a lower education level, a watchful waiting approach, medical comorbidities, and a lower HRQoL. This underscores the importance of attention for these factors during consultations.</p>