Objective Delirium duration is predictive of long-term cognitive impairment (LTCI) in Intensive Care Unit (ICU) survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and LTCI, we conducted this exploratory investigation of the associations between delirium duration, brain volumes and LTCI. Design, Setting, and Patients A prospective cohort of medical and surgical ICU survivors with respiratory failure or shock. Measurements Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and three-month follow-up. Delirium was evaluated using the Confusion Assessment Method for the ICU; cognitive outcomes were tested at three- and twelve-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results A total of 47 patients completed the MRI protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio (VBR) at hospital discharge [0.76, 95% confidence intervals (CI) (0.10, 1.41); p=0.03] and at 3-month follow-up [0.62 (0.02, 1.21), p=0.05]. Longer duration of delirium was associated with smaller superior frontal lobe [−2.11 cm3 (−3.89, −0.32); p=0.03] and hippocampal volumes at discharge [−0.58 cm3 (−0.85, −0.31), p<0.001] – regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher VBR) at three months was associated with worse cognitive performances at twelve months [lower RBANS battery score −11.17 (−21.12, −1.22), p=0.04]. Smaller superior frontal lobes, thalamus, and cerebellar volumes at three months were associated with worse executive functioning and visual attention at twelve months. Conclusions These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to three months after discharge, and that smaller brain volumes are associated with LTCI up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.