It is well-established that stress impairs immunity, however, the precise underlying mechanisms remain elusive. We discovered that stress modulates the expression levels of acute-phase proteins (APPs), which broadly regulate physiological processes including innate immunity and homeostasis maintenance. APPs are traditionally associated with the inflammatory response and are commonly used as indicators for inflammation (e.g., CRP). We found that stress on its own can also affect APPs levels and that stress preceding an inflammatory challenge disrupts the typical APPs response. Importantly, we found that this influence is not mediated through the classical hypothalamic-pituitary-adrenal (HPA) axis but rather involves direct sympathetic inputs to the liver. Thus, our study identifies a novel pathway through which stress can impact immunity.