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We report a case of unilateral serous choroidal effusion in a patient without prior glaucoma surgeries that developed within 1 week of starting topical dorzolamide. A Caucasian female in her 60s with a history of severe primary open-angle glaucoma in the left eye without prior glaucoma surgeries developed irritation and subsequently blurry vision in her left eye within 1 week of starting topical dorzolamide 2% in the left eye only. Funduscopic exam and B-scan ultrasound demonstrated a serous choroidal effusion in the nasal and temporal periphery. After discontinuing dorzolamide and initiating prednisolone and cycloplegic agents, the choroidal effusions fully resolved after 2 weeks, and vision returned to baseline. Choroidal effusion can occur as a result of an idiosyncratic reaction to topical dorzolamide even in patients without prior glaucoma surgeries. Immediate cessation of dorzolamide and treatment with steroid and cycloplegic agents result in good vision recovery for dorzolamide-induced choroidal effusion.