Every year, 40 000 patients are treated in Swedish intensive care units (ICUs). Over 35% of all ICU patients suffer from sepsis, with high mortality rates and multiple organ involvement. However, most survive. This group of patients suffers from various problems that make it difficult to return to their pre-infection life. Many patients describe affected cognitive function after sepsis but the association between sepsis and later cognitive problems is not well studied. The group's partners have found in animal studies that the level of a bodily inflammatory substance, High Mobility Group Box 1 (HMGB1), is elevated for months after sepsis and associated with cognitive problems. Cognitive function was restored with administration of HMGB1 monoclonal antibodies. HMGB1 administration to healthy mice caused cognitive dysfunction. The association has not been studied in humans. The project includes prospective cohort studies of ICU patients with/without sepsis, in order to follow HMGB1 levels and cognitive function one year after discharge from the ICU. The main questions in the project are whether there is a connection between severe sepsis, delirium and later cognitive dysfunction and whether cognitive dysfunction is linked to prolonged inflammation with elevated levels of HMGB1. If prolonged inflammation with HMGB1 elevation late in the course is linked to late cognitive problems after sepsis in humans, the findings may lead to future clinical trials of immunomodulatory therapy.