Aim To analyze the prognostic impact of short‐term changes in the intensity of delirium in association or not with sepsis. We also aimed to analyze if s100B, a serum protein derived from astrocytes related to cerebral damage, could be a marker of delirium or sepsis. Methods We included 47 patients with acute delirium and sepsis, 36 with delirium and no evidence of infection, and 36 patients with sepsis without delirium. The diagnosis of delirium was established by the Confusion Assessment Method. To evaluate delirium, we recorded the following characteristics on the first and third day after admission: level of consciousness, orientation, attention, hallucinations, psychomotor activity, language and disorganized thinking. Results In 53 patients, delirium improved during hospitalization with 3.8% of mortality, whereas in the 30 patients in which delirium did not improve or worsened, 50% died during hospitalization. The improvement on the third day of consciousness, orientation, attention and disorganized thinking was related to a better long‐term survival. s100B and inflammatory markers tumor necrosis factor‐α, interleukin‐6, interleukin‐10 and interferon‐γ were increased in patients with sepsis and confusion when compared with control participants; furthermore, s100B, interleukin‐6 and interferon‐γ were increased in septic patients without confusion, but also in delirious patients without sepsis. Conclusions The main factor related to mortality was the recovery from delirium during hospitalization. We found increased s100B serum levels in patients with delirium, but also in septic patients without delirium. This increase was not related to mortality. Geriatr Gerontol Int 2017; 17: 1161–1167.