The COVID-19 pandemic has placed tremendous burdens on healthcare workers (HCWs), accounting for over 1.4 million HCW infections and 10% of global fatalities. HCWs faced elevated infection risk, psychological distress, long working hours, fatigue, stigma, and violence. While vaccines are pivotal in reducing severe illness, HCW vaccine hesitancy, given their role as advocates, jeopardizes vaccination coverage global goals and healthcare systems. Addressing this vaccine uptake is imperative through education, transparent communication, and support to safeguard HCWs’ safety and pandemic containment. This study assessed COVID-19 vaccination uptake among frontline HCWs in Kaduna State, Nigeria, and its impact on morbidity and mortality. Utilizing a descriptive cross-sectional approach, we analyzed secondary data from the Surveillance Outbreak Response Management and Analysis System (SORMAS). The study encompassed HCWs in Kaduna State, excluding pregnant and lactating individuals, following national guidelines. Among 8095 HCWs tested for COVID-19, most were aged 31-40 years (35%), female (60.2%), and urban residents (70.3%). COVID-19 vaccination uptake was low at 17.4%, with 82.6% unvaccinated. COVID-19 infection was significantly associated with vaccination (p = 0.039). Although unvaccinated participants exhibited a higher mortality rate (60%) than vaccinated ones (40%), this difference was not statistically significant (p = 0.209). In conclusion, this study unveiled insufficient vaccination uptake among HCWs, potentially impeding pandemic response. While vaccination seemed to positively impact disease outcomes, it didn’t significantly affect the infection risk. Addressing HCW vaccine hesitancy remains critical for achieving immunization goals and ensuring healthcare system safety. Keywords: Covid-19, Vaccines, Vaccination uptake, Healthcare workers (HCW), Infection.