Background and Aims: Patients with alcohol-related cirrhosis (ALD) are prone to infection. Circulating neutrophils in ALD are dysfunctional and predict development of sepsis, organ dysfunction and survival. Neutrophil granules are important effector organelles containing a toxic array of microbicidal proteins, whose controlled release is required to kill micro-organisms whilst minimising inflammation and damage to host tissue. We investigated the role of these granular responses in contributing to immune disarray in ALD. Methods: Neutrophil granular content and mobilisation was measured by flow cytometric quantitation of cell-surface/intracellular markers, [secretory vesicles (CD11b), secondary granules (CD66b) and primary granules (CD63; myeloperoxidase)] before and after bacterial stimulation in 29 patients with ALD cirrhosis compared to healthy controls (HC). ImageStream Flow Cytometry characterised localisation of granule subsets within the intracellular and cell-surface compartments. The plasma cytokine environment was analysed using ELISA/Cytokine Bead Array. Results: Circulating neutrophils were primed in the resting state with upregulated surface expression of CD11b (p=0.0001) in a cytokine milieu rich in IL-8 (p<0.001) and lactoferrin (p=0.035). Neutrophils showed exaggerated mobilisation to the cell surface of primary granules at baseline (p=0.001) and in response to fMLP (p=0.009) and E. coli (p=0.0003). There was no deficit in granule content or mobilisation to the cell membrane in any granule subset observed. Paradoxically, active alcohol consumption abrogated the hyper-responsive neutrophil granular responses compared to their abstinent counterparts. Conclusions: Neutrophils are pre-primed at baseline with augmented effector organelle mobilisation in response to bacterial stimulation; neutrophil degranulation is not a mechanism leading to innate immunoparesis in ALD.