This study assessed the functionality of selected aspects of innate immunity in prematurely born infants with very low birth weight and examined whether the differences in their activity depend on the degree of a newborn’s level of maturity and if this may affect the risk of late-onset sepsis (LOS). Immunological tests (absolute number of individual monocyte subpopulations and IRA B cells, expression of PD-1 receptor, intracellular expression of interleukin 1β (IL-1β), inflammasome function) were performed in all study participants on the 5th day of life (n=76) as well as in newborns who developed LOS (n=39). On the 5th day of life, a correlation was observed between gestational age and the total amount of all monocytes as well as all the subtypes: classical and intermediate. In addition, lower expression of IL-1β in monocytes may be an independent risk factor for the development of LOS. During LOS, a greater number of intermediate and non-classical monocytes, inflammasome activation features, and, in moremature newborns, a higher intracellular expression of IL-1β, which may indicate higher activity of the Toll-like receptors associated with higher gestational age, were observed. The percentage of IRA B cells was comparable at both time points. The level of PD-1 receptor expression depended on the stage of maturation of monocytes, antenatal steroid treatment, degree of prematurity and occurrence of systemic infection as well as its complications: septic shock and death. It was hypothesized that induction of apoptosis from the PD-1 receptors may be responsible for limiting proinflammatory activity of monocytes.