Case summary A 6-year-old male castrated Siamese cat was referred for acute-onset blindness and mydriasis. Physical examination revealed serous retinal detachment with panuveitis and systemic hypertension. Abdominal ultrasound showed suspected dilation of the cisterna chyli and abdominal lymphadenopathy. Aspirates of mesenteric lymph nodes revealed intrahistiocytic yeast organisms with mild-to-moderate pyogranulomatous inflammation. Fungal culture and ITS1 sequencing of the lymph node aspirates confirmed infection with Histoplasma capsulatum. PCR performed on whole blood was positive for Bartonella henselae and Bartonella clarridgeiae, and Toxoplasma gondii IgG and IgM antibodies were detected in serum. The cat was prescribed prednisolone (0.5 mg/kg PO q24h), itraconazole (10 mg/kg PO q24h), clindamycin (13 mg/kg PO q12h), amlodipine (0.625 mg PO q24h), prednisolone acetate 1% drops (q6h) and ophthalmic lubricant for both eyes (q6h). The cat was doing well at home after 2 weeks of prednisolone, itraconazole and clindamycin administration, and no abnormalities were detected on repeat abdominal ultrasound 3 months later. The retinal detachment showed mild-to-moderate improvement at that time, but vision was not regained. Relevance and novel information This is the first report of coinfection of H capsulatum, T gondii, B henselae and B clarridgeiae in an indoor-only cat living in a H capsulatum non-enzootic area with no known travel history.