Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition associated with significant morbidity, including psychiatric disease such as depression. The prevalence of depression, and the effect of anti-tumor necrosis factor alpha (TNFα) therapy on cognitive and somatic symptoms is not yet fully understood. Objectives: To examine (1) the prevalence of depression, using the validated Beck Depression Inventory-II (BDI-II) in patients with IBD, and (2) the association between depression with anti-TNFα therapy, disease type, disease activity, CRP, anemia, fatigue, and health related quality of life (HRQoL). Methods: Using a cross-sectional design in adult outpatients with a confirmed diagnosis of IBD, participants completed questionnaires assessing depression (BDI-II), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)), andHRQoL (Short IBDQuestionnaire (SIBDQ)). The BDI-II is categorized into minimal (0-13), mild (14-19), moderate (2028) and severe (29-63) depression, and can be grouped into cognitive and somatic domains. Demographic characteristics were also obtained. Results: Two hundred and ninety-five patients (50.8% female) with IBD (69.8% CD), including 55.2% anti-TNFα were enrolled. The prevalence of mild (14.2%), moderate (11.5%), and severe (7.5%) depressive symptoms in IBD patients was higher than reported population prevalences (13.7%; 7.1%; 2.1%, respectively). The proportion of depressed female patients (37.3%) was not statistically different to that of depressed males (28.9%, p=0.13). There was a trend seen in mean BDIII scores between CD (12.4±10.0) and UC (10.2±8.4, p=0.07) patients. Anti-depressant use (17.1±11.8, p=0.002), clinical assessment of active disease (15.0±10.0, p<0.001), and steroid use (14.1±11.0, p=0.043) were associated with a higher mean depression inventory, but anti-TNFα use (12.4±9.8, p=0.17), high CRP (13.5±9.3, p=0.29), and anemia (13.4±10.6, p=0.25) were not significantly different. In depressed patients, mean HRQoL scores (SIBDQ 3.7±1.4) were significantly lower than non-depressed patients (5.2±1.5, p<0.001). Somatic scores were significantly higher in IBD patients with features of active disease (7.7±4.2 vs 5.1±3.7, p=0.005) or high CRP (7.4±4.0 vs 5.8±4.3, p<0.001). Conversely, those with antiTNFα therapy had significantly more cognitive depressive symptoms (6.3±6.1 vs 4.9±5.7, p=0.047) than those not on biologics, but not somatic symptoms (6.2±4.1 vs 6.0±4.2, p= 0.69). Conclusions: Prevalence of depression in adult outpatient IBD practice is significantly higher compared with the general population, especially in those patients with active disease. AntiTNFα therapy was associated with increased cognitive, but not somatic depressive symptoms.