Abstract: Background – In canine leishmaniosis (CanL), high antibody titer corresponds with clinical signs, except in dogs with papular dermatitis or uveitis where serology is often low or negative. Objectives – To describe the clinical findings of dogs with leishmaniosis but low or negative serology. Animals – 27 client-owned dogs with leishmaniosis. Methods – Retrospective case-series. Results – The 27 dogs were grouped by their main clinical presentation: gastrointestinal (9), dermatologic (8), hematologic (6), musculoskeletal (2), neurological (1), and renal (1). Five dogs were on immunosuppressive therapy. Serology was negative in 15 dogs and low in 12. CanL diagnosis was based on a combination of cytology (lymph nodes= 6, spleen= 6, liver= 3, cutaneous lesions= 2, conjunctiva= 2), PCR (blood= 3, lymph nodes= 2, bone marrow= 2, CSF= 1, synovial fluid= 1), and bone marrow (5), intestinal (2), and skin biopsy (1). Dogs were treated with allopurinol and meglumine antimoniate (21) or miltefosine (5); one dog received only allopurinol. Most (20/27) responded well, and serology remained low or negative in dogs with favorable outcomes. Conclusions and Clinical Importance – Some dogs with clinical active leishmaniosis exhibit low or negative serology, which could be due to concurrent immunosuppression, high numbers of immune-complexes, or infections with different Leishmania species inducing antibodies not detected by the assays used for Leishmania infantum. Additionally, some dogs may develop clinical signs despite mounting a Th1 immune response with low antibody production. When CanL is suspected, but serology is negative or low, further investigations are warranted.