Many of the pharmacological agents used in clinical practice can potentially cause some adverse reaction in any part of the pulmonary system. As more drugs are being discovered, the list of pulmonary toxicities also is getting longer. We present a case of a 25 year old man, known case of Ankylosing spondylitis, who presented with orthopnea and was found to have pleuro-pericardial effusion. Investigations revealed exudative eosinophilic fluid with low adenosine deaminase levels. Thoracoscopic pleural biopsy showed dense eosinophilic infiltration of the pleura. Infection and malignancy were ruled out by relevant tests. A diagnosis of drug induced pleuro-pericardial effusion was made by exclusion of other causes.. Etanercept was witheld and patient was started on steroids after which he showed significant improvement on follow up. We suggest Etanercept be considered in the growing list of drugs causing pleuro-pericardial effusion. To our knowledge, a case of pleuro-pericardial effusion with eosinophilic pleural infiltration due to Etanercept specifically has not been previously described.