Aspergillus infections are among the most feared opportunistic infections in humans. These organisms are ubiquitous in nature; protection against infection is usually provided by anatomical barriers and by the immune system. Tissue invasion by Aspergillus is uncommon, occurring primarily in the setting of immunosuppression. The prognosis of invasive aspergillosis is very poor. Although it is widely recognised that critically ill patients in the Intensive Care Unit (ICU) are at risk for nosocomial infections, it is not generally appreciated that such patients may also be at risk for opportunistic infections usually seen only in immunocompromised patients. This might be explained by a biphasic immunological pattern during sepsis: an early hyperinflammatory phase followed by an anti-inflammatory response, leading to a hypo-inflammatory state, the so-called compensatory anti-inflammatory response syndrome (CARS or immunoparalysis). We describe four patients admitted to our ICU for various reasons, without a history of abnormal immune function, who developed invasive pulmonary aspergillosis. We hypothesise that the occurrence of these opportunistic infections in our patients may have been due to immunoparalysis, and that perhaps all ICU patients with sepsis and multiple organ dysfunction syndrome (MODS) may be at risk for opportunistic infections such as aspergillosis as a result of this syndrome. Physicians treating critically ill patients in the ICU should be aware of the CARS/immunoparalysis syndrome and its potential to cause opportunistic infections, even in patients with normal immune function prior to ICU admission.