Treatment of severe sepsis and septic shock often focuses on resolving immediate life-threatening problems related to infection (source control, antibiotics) and providing circulatory, ventilatory and other organ support. Neurologic complications, such as sepsis-associated encephalopathy, frequently occur in septic patients and are associated with higher mortality and long-term complications. As case fatalities and overall mortality continue to decline, long-term cognitive problems are becoming more common among survivors. Although the aetiology of septic encephalopathy has not been clearly established, systemic inflammation appears to play a key role in altering both the blood–brain barrier permeability and amplifying the inflammatory response. Several new therapies are now aimed at reducing systemic inflammation. These may eventually play a role in reducing neurologic complications related to the acute pathophysiology of sepsis and may be able to reduce early cerebral dysfunction with the goal of reducing long-term neurologic complications. Coupled plasma filtration adsorption is an extracorporeal therapy aimed at the non-specific removal of cytokines and mediators involved in systemic inflammation and immune suppression by the use of plasma filtration coupled to an adsorbent resin cartridge with high affinity for many cytokines and mediators. Several cytokines that are removed by coupled plasma filtration adsorption have also been implicated in blood–brain barrier permeability, leucocyte recruitment and amplification of the inflammatory response. Current studies are ongoing to determine whether treatments such as coupled plasma filtration adsorption may also be beneficial in reducing long-term neurologic complications.