Introduction: Acquired methemoglobinemia has been well known as an adverse side-effect following treatment with Dapsone for prophylaxis against Pneumocystis jirovecii pneumonia (PCP) in HIV positive patients. Treatment for non glucose-six phosphate dehydorgenase (G6PD) deficient patients includes the administration of intravenous methylene blue and the removal of the offending agent. Although not well described, a rebound increase of methemoglobin levels can occur upwards of 24 hours following initial treatment. Case: A 41-year old African American male with long standing HIV secondary to blood transfusion presented with a three-week history of progressing dyspnea and generalized weakness. Patient had a history of allergy to sulfonamides and was on Dapsone for PCP prophylaxis. On admission initial laboratory data revealed white blood cell count 4.0 k/mcl with 1% band forms, hemoglobin 11.3 g/dL, hematocrit 35.8%, platelet count 232 K/mcL. Upon further workup there appeared to be interstitial reticulation within the right lung base and extensive chronic fibrotic changes on imaging, and broncho-lavage cultures revealed PCP pneumonia prompting intravenous Pentamidine therapy. With initial decline of respiratory status, the patient was placed on noninvasive mechanical ventilation and arterial blood gas (ABG) measurements were obtained. ABG's revealed pH of 7.519, PaO2 of 139 mmHg on 100% of FiO2, pCO2 of 26.6 mmHg, HCO3 of 21.2 mmol/L, hemoglobin oxygen saturation of 74.1% and a methemoglobin level of 23.2%. His respiratory status acutely declined requiring intubation and transfer to the intensive care unit with initiation of methylene blue. Patient's methemoglobin level initially increased to 30.2% with a worsening anemia reaching a hemoglobin of 9.3 gm/dL. Treatment was suspected to be ineffective prompting suspension of treatment and G6PD evaluation. Ascorbic acid therapy was alternatively started pending G6PD and hemolysis evaluation, ultimately revealing normal studies. Methylene blue was reinitiated reaching a methemoglobin level of 4.1% with increasing oxygen hemoglobin saturation of 92.4%. ABG's were serially obtained with a rising methemoglobin level from 4.1% to 13% with a decreasing oxygen hemoglobin saturation of from 92.4% to 84.6%. Methylene blue was continued for an additional 24 hours with methemoglobin levels ultimately reaching 1.9% with oxygen hemoglobin saturation of 94.4%. The patient later refused further treatment ultimately resulting in palliative care. Discussion: In HIV patients presenting with respiratory distress, aside from an infectious etiology, acquired methemoglobinemia must be kept on the differential secondary to prophylactic treatment against opportunistic infections. This case illustrates how a rebound increase in methemoglobin levels may occur following initial resolution. Rebounding may increase to symptomatic levels beyond 20%, and can rise greater than 40%, which is associated with high mortality rates. This requires serial monitoring of blood gasses and repeated treatment beyond initial therapy. Currently there are no guidelines to suggest the frequency of monitoring post therapy. It is essential for treating clinicians to be aware of this uncommon, yet serious trend, requiring careful monitoring for relapse of levels and worsening respiratory function.