X-Linked hypophosphataemic rickets (XLH) is a rare multisystemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls.The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995-2016), along with a non-XLH cohort matched (1:4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to Index of Multiple Deprivation (IMD).There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine (OR 3.46 [95% CI: 1.44-8.31]) and neurological (OR 3.01 [95% CI: 1.41-6.44] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 [95%CI: 1.47-5.92]. Distribution of IMD among XLH cases indicated greater deprivation than the general population.We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients.