Introduction: Background: Human Granulocytic Anaplasmosis (HGA), caused by the bacteria Anaplasma phagocytophilum, is a tick-borne disease, with a wide spectrum of clinical presentation. Respiratory failure and the Acute Respiratory Distress Syndrome (ARDS) are very uncommon manifestations. We report a case of acute anaplasmosis in a previously healthy immunocompetent woman who developed ARDS and respiratory failure. Case: A 49 year old female with no significant past medical history presented to her local hospital three days after returning from Boston, MA, with complaints of fevers, neck pain and body aches. She lived in a rural area of Pennsylvania. Her initial blood work revealed pancytopenia, eosinophilia, and transaminitis. Chest radiograph demonstrated bilateral airspace opacities without evidence of volume overload. Within 12 hours of admission, she developed hypoxemic respiratory failure requiring mechanical ventilation. She was started on vancomycin, piperacillin-tazobactam and doxycycline on admission and transferred to our facility for further care. Bronchoalveolar fluid showed a lymphocytic predominance, and testing for viral, fungal and bacterial respiratory pathogens was negative. Blood tests for Lyme, Ehrlichia and Babesia were also negative. Serum IgM and IgG for anaplasma were normal, but Anaplasma DNA was later detected by real-time PCR. Treatment was continued with doxycycline, with rapid clinical and radiographic improvement. She was extubated after three days of mechanical ventilation. Discussion: Most adults with HGA present with a minor acute febrile illness. Elderly or immunosuppressed patients may have a more fulminant infection. Common laboratory abnormalities include elevated transaminases, leukopenia and thrombocytopenia. Common clinical presentations include nausea/vomiting, malaise or aseptic meningitis. ARDS and respiratory failure from HGA infection is very uncommon. Due to the high suspicion for tick-borne illness, she was treated appropriately with doxycycline and her respiratory failure quickly resolved. Her positive PCR and constellation of clinical and laboratory findings confirm the diagnosis of HGA with acute ARDS.