Pain and depression are associated with both physical and mental fatigue independently of comorbidities and medications in primary Sjögren’s syndrome. On behalf of the UK primary Sjögren’s Syndrome Registry Objectives  To report on fatigue in patients from the United Kingdom primary Sjögren’s syndrome (pSS) registry identifying factors associated with fatigue and robust to assignable causes such as comorbidities and medications associated with drowsiness. Methods From our cohort (n = 608), we identified those with comorbidities associated with fatigue, and those taking medications associated with drowsiness. We constructed dummy variables, permitting the contribution of these potentially assignable causes of fatigue to be assessed. Using multiple regression analysis, we modelled the relationship between Profile of Fatigue and Discomfort physical and mental fatigue scores and potentially related variables. Results Pain, depression and daytime sleepiness scores were closely associated with both physical and mental fatigue (all p ≤ 0.0001). In addition, dryness was strongly associated with physical fatigue (p ≤ 0.0001). These effects were observed even after adjustment for comorbidities associated with fatigue or medications associated with drowsiness. Conclusions  These findings support further research and clinical interventions targeting pain, dryness, depression and sleep to improve fatigue in patients with pSS. This finding is robust to both the effect of other comorbidities associated with fatigue and medications associated with drowsiness. Introduction Primary Sjögren’s syndrome Recommendations Our data confirm the importance of fatigue symptoms— both mental and physical—to patients with pSS and permit identification of factors contributing to fatigue including other comorbidities and medications associated with drowsiness. Given the wide variety of potential factors contributing to fatigue, we support the view that a multidisciplinary approach is essential for the clinical management of fatigue in pSS.32 We observe that many patients with pSS are taking multiple medications and we recommend a medication review be undertaken to identify drowsy medications which could be contributing to fatigue. If these medications are discontinued, then a review should be arranged and if the fatigue does not improve, then treatment of comorbidities should be considered. However, as pain is a major contributor of both mental and physical fatigue, the contribution of some pain-modifying medications may be beneficial, despite their association with drowsiness. Patients with pSS should be tested for common comorbidities which can contribute to fatigue, including anaemia or hypothyroidism and offered appropriate treatments. We recommend screening for depression and anxiety and offering patients appropriate interventions to address these symptoms. Non-pharmacological interventions (such as talking therapies) may reduce the need for antidepressants and anti-anxiolytics, many of which are associated with drowsiness. We recommend that patients undergo a more detailed sleep assessment in order to screen for a primary sleep disorder. Patients identified with conditions such as obstructive sleep apnoea should be offered assignable causes such as Continuous Positive Airway Pressure (CPAP) treatment. Interventions such as cognitive behavioural therapy for insomnia (CBT-I) are a first-line treatment for insomnia associated with other medical conditions and may prove beneficial to patients with pSS. Patients with pSS should be offered appropriate pain management interventions. If pain is associated with poor sleep, then CBT-I with a pain adjunct has been suggested as a feasible treatment. Finally, in the absence of good evidence to support effective drug treatments, fatigue interventions in pSS might focus on a multidisciplinary approach incorporating activity management, graded exercise/ activity and CBT. See full report of this study. FIND OUT MORE ABOUT SJOGREN'S SYNDROME HERE: List of Sjogren's Syndrome Symptoms Increased prevalence of Sjogren's syndrome in high level chromium soils Study suggests future way to treat chronic eye problems and lymphoma in Sjogren's Syndrome. How Sjogren's is diagnosed Dry eye found in over 85% of Sjogren’s patients