Systemic capillary leak syndrome (SCLS) is a rare disorder with a high mortality rate, characterized by rapidly developing edema, weight gain and hypotension, hemoconcentration and hypoproteinemia. This syndrome is caused by sudden, reversible capillary hyperpermeability with a rapid extravasation of plasma from the intravascular to the interstitial space. Even though SCLS has been suggested to be the pathogenic mechanism for the pulmonary toxicity of gemcitabine (GCB), a new deoxycytidine analogue with structural similarities to cytosine arabinoside, a direct correlation between GCB and SCLS has never been reported. We describe a case of repeated SCLS after GCB administration in a 51-year-old male with locally-advanced non-small-cell lung cancer treated with a combination of cisplatin and GCB. The detection of GCB-induced SCLS supports the hypothesis that SCLS could be the pathogenic way of GCB pulmonary toxicity. This finding can help to better understand and treat the potentially deadly GCB-related acute respiratory distress syndrome that is being recognized.