The pathological processes underlying Acute Rheumatic Fever (ARF) and its progression to Rheumatic Heart Disease (RHD) are poorly understood, hindering the development of therapeutics to interrupt severe and progressive disease. Our immune phenotyping in cross-sectional ARF studies points to perturbation in the T cell compartment during cytokine mediated inflammation as a possible pathway for therapeutic intervention. To extend these insights, this study profiled immune features in 11 NZ ARF cases longitudinally over 6-months. ARF cases were enrolled in a pilot trial of hydroxychloroquine treatment (HYDRxARF) and compared with controls from adjacent studies (hospitalised RHD, healthy, and those receiving secondary prophylaxis for ARF in the community). The inflammatory cytokine IL-6, immunoglobulin IgG3, and chemokine CCL5 were all elevated in ARF and normalised over the 6-months, supporting involvement in the acute disease phase. Of note, CCL5 produced by immune cells from ARF patients after stimulation with Group A Streptococcus correlated with serum CCL5, suggesting local circulating immune cell production of this chemokine occurs in ARF. New insights were also made into T cell perturbation, with reduced markers of T cell activation and increases in T regulatory cells over the 6-month time course. While this study involves only a small number of participants, the longitudinal perspective demonstrates reductions in inflammatory antibodies and cytokines together with rebalancing of the T cell compartment associated with disease resolution. Overall, these findings suggest that immune modulating therapies that encourage resolution of inflammation are worthy of further investigation as ARF treatments.