Abstract: Background Despite initial favorable responses to cytotoxic chemotherapy, most canine patients with B-cell lymphoma relapse within a year. However, a subset experience prolonged remission. Objectives We aimed to discover putative transcriptional and circulating biomarkers associated with remission duration. Animals Eighteen client-owned canine patients with a confirmed diagnosis of naïve, intermediate-to-large, B-cell lymphoma undergoing CHOP chemotherapy (vincristine, cyclophosphamide, doxorubicin, prednisone). Methods Patients were prospectively enrolled. Plasma, whole blood, and RNA from nodal aspirates were acquired prior to CHOP. Immune transcriptional profiling was undertaken utilizing the NanoString nCounter Canine IO panel, and data were analyzed on the ROSALIND platform. Serologic profiling was undertaken using ELISA and Luminex assays. Remission duration and outcome were recorded, establishing a minimally invasive biobank with linked hematologic, cytologic, immunophenotypic, and clinical metadata. Results Median time to progression (TTP) was 262.5 days for all patients, with 5 patients retaining remission over 2 years. Immune transcriptional profiling identified 47 differentially expressed genes (p< 0.05) between the five patients with significantly prolonged remission compared to the five patients with the shortest remission durations (log-rank p=0.0017). T-cell transcripts and angiogenic markers were enriched in dogs with prolonged and short remissions respectively. Increased circulating VEGFA, IL-6, and neutrophil: lymphocyte were documented in dogs with short remissions. Conclusions Our data revealed early evidence supporting favorable associations of T-cell signatures with longer remissions and pro-angiogenic activity associated with shorter remissions following CHOP for canine B-cell lymphoma.