Background: Home parenteral nutrition (HPN) provides life‐sustaining treatment for people with chronic intestinal failure (CIF). Poor quality of life is reported in association with the burden of HPN and the underlying condition leading to intestinal failure (IF). However, levels of negative affect (NA), incorporating anxiety and depression, have not been reported in CIF. This study examined the occurrence and risk factors for NA in a large CIF population using the validated Hospital Anxiety & Depression Scale (HADS) and Multidimensional Scale of Perceived Social Support (MSPSS) questionnaires. Methods: A survey pack including HADS and MSPSS were distributed to patients managed by a specialist IF center. Data from these measures were analyzed against factors including underlying disease, length of time receiving HPN, employment status, and demographics. Results: Of 85 patients who completed this study, 56% had clinical levels of anxiety and/or depression. Linear regression analysis confirmed significant correlations between social support and HADS scores, with poorer perceived social support associated with higher levels of NA (−0.26 MSPSS + 33.24; R2 = 0.29; P < .0001). There were also significant associations between unemployment and higher anxiety (P = .004), depression (P = .008), and NA scores (P = .003). By contrast, there were no significant associations between patient age, duration of time receiving parenteral nutrition, pathophysiological mechanisms of CIF, and NA levels. Conclusions: Clinical anxiety and depression are common, affecting more than half of patients with CIF. Patients with poor social networks and those of working age who have ceased employment are particularly vulnerable and should be prioritized for psychological support because of their elevated risk.