In this mini-review, we will discuss recent findings that implicate neutrophil infiltration and function in establishing a metabolic environment to facilitate efficient pathogen clearance. For decades, neutrophils have been regarded as short lived, nonspecific granulocytes, equipped with toxic antimicrobial factors and a respiratory burst generating ROS. Recent findings demonstrate the importance of HIF signaling in leukocytes and surrounding tissues during inflammation. Here, we will review the potential mechanisms and outcomes of HIF stabilization within the intestinal mucosa.