Apolipoprotein A-I (APOA1), the major protein of high-density lipoproteins, has anti-inflammatory functions. APOA1 is primarily produced in the liver; however, it is not known whether neutrophils are a cellular source. Here, we assessed whether human neutrophils express APOA1. Peripheral blood and bronchoalveolar lavage fluid (BALF) were obtained from healthy volunteers (HVs) and asthmatics. Peripheral blood neutrophils from HVs expressed APOA1 at both the mRNA and protein levels, while confocal microscopy demonstrated that APOA1 was localized to a unique population of intracytoplasmic granules. In HVs and asthmatics, APOA1 was preferentially expressed by neutrophils with high side-scatter (SSChigh) in blood and BALF. Furthermore, APOA1+ SSChigh neutrophils were characterized as a population with high levels of caspase-3/caspase-7 activation and CCR5 expression. Since APOA1 has anti-inflammatory functions, this suggests that APOA1 expression by neutrophils may represent a mechanism to attenuate excessive inflammatory responses in health and disease.