During the 2009-2010 winter season, the new pandemic influenza A/H1N1 virus (S-OIV) was responsible for 1,334 hospitalized severe infection cases including 312 (23.4%) deaths in metropolitan France. In the Champagne-Ardenne area (north eastern) this new epidemic strain was detected in the respiratory samples of 14 severe S-OIV infection cases resulting in 5 deaths. Here we report two of these 14 cases who were suffering from a bilateral pneumonia related to S-OIV infection and who were hospitalized in the Intensive Care Unit (ICU) of the Reims University Medical Centre during December 2009. These two patients were male with at least one known risk factor for severe S-OIV infection (chronic obstructive pulmonary disease (COPD) and morbid obesity, respectively); the COPD patient developed an acute respiratory distress syndrome. The etiological diagnosis of S-OIV infection was performed by use of a real time RT-PCR (rRT-PCR) assay allowing the detection of all the known human influenza A viruses (rRT-PCR targeting the influenza gene M) and of the new influenza A/H1N1 pandemic strain. This rRT-PCR assay was positive in bronchoalveolar lavage samples taken from the two patients, whereas the nasal swab (using Virocult® collection system) appeared to be positive for only one of them. For both patients, a presumptive treatment combining oseltamivir and broad-spectrum antibiotics was started at the time of hospital admission, 24 hours at least before obtaining the results of the virological and bacteriological analyses. These two patients did not develop any secondary bacterial pneumonia and their clinical outcome was good after one and six weeks of hospitalization in ICU, respectively.