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Background: Zinc deficiency (ZD) in Crohn's disease (CD) is considered a frequent finding and may exacerbate CD activity. ZD is associated with depression in non-CD patients. We aimed to assess the prevalence of ZD in CD patients in clinical remission, its association with mood disturbances and to analyze a potential impact on future disease course. Methods: Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years (n = 47) were compared with those from patients developing complications (n = 50). Baseline symptoms of depression and anxiety were measured with the Hospital Anxiety and Depression scale. Results: Mean zinc level in the 97 patients (40.4 ± 15.7 years, 44.3% males) was 18.0 ± 4.7 μmol/l. While no ZD (<11 μmol/l) was observed, we found low zinc levels (<15.1 μmol/l) in 28 patients (28.9%). Males had higher zinc levels compared with females (19.4 ± 5.7 versus 16.8 ± 3.3, p = 0.006). Patients with low zinc levels more often reported depression symptoms compared with patients with higher levels (27.3 versus 9.4%, p = 0.047). In a multivariate analysis, zinc levels were an independent negative predictor for depression symptoms [odds ratio (OR) 0.727, 95% confidence interval (CI) 0.532–0.993, p = 0.045]. Zinc levels of patients with a complicated disease course were not different from those of patients without (17.7 ± 4.3 versus 18.3 ± 5.1, n.s.). Baseline zinc levels did not predict disease outcome regardless of ATG16L1 genotype. Conclusion: Low–normal zinc levels were an independent predictor for the presence of depression symptoms in CD patients. Zinc levels at baseline did not predict a complicated disease course, neither in CD patients overall, nor ATG16L1T300A carriers. [ABSTRACT FROM AUTHOR]