Calorie restriction (CR)-induced weight loss has been shown to lower the risk of chronic disease in obese individuals. Although the mechanisms that link weight loss to disease risk reduction remain unclear, evidence suggests adipokines may play a role. What has yet to be determined, however, is the dose-response effect of body weight loss and visceral fat mass loss on adipokines. Accordingly, this review examines how varying degrees of CR-induced weight loss (i.e., >10%, 5–10%, and <5% from baseline) impact plasma levels and expression of adiponectin, leptin, resistin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and retinol-binding protein 4 (RBP-4). The dose-response relationship between visceral fat mass loss and adipokine profile improvement will also be explored. Results from this review demonstrate that even mild weight loss induced by CR may have beneficial effects on leptin levels, but it has no clear impact on adiponectin, resistin, IL-6, IL-8, MCP-1, or RBP-4 concentrations.