Neutrophils are among the fastest-moving immune cells. Their speed is critical to their function as ‘first responder’ cells at sites of damage or infection and it has been postulated that the neutrophils’ unique segmented nucleus functions to assist their rapid migration. Here, we tested this hypothesis by imaging primary human neutrophils traversing narrow channels using custom-designed microfluidic devices. Individuals were given intravenous low-dose endotoxin to elicit the recruitment of neutrophils into the blood with a high diversity of nuclear phenotypes, ranging from hypo- to hyper-segmented. Both by sorting on neutrophils from the blood using markers that correlate with lobularity, and by directly quantifying the migration of neutrophils with distinct lobe numbers, we found that neutrophils with 1-2 nuclear lobes were significantly slower to traverse narrower channels, compared to neutrophils with >2 nuclear lobes. Thus, our data show that in primary human neutrophils nuclear segmentation provides a speed advantage during migration through confined spaces.