Abstract Objectives: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. Methods: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. Results: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). Conclusion: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU. Objectives (FI rates . (NICU) Thus indicators Methods 1510 1 510 1,51 201 2022 data sex weight age analyzed Results 3 12 2 1. 1000 000 1,00 52.9 529 52 9 (52. , %) 78.9 789 78 (78. 727 72 7 72. 2018 333 33. 75 stay nutrition broadspectrum broad spectrum occurrence th cephalosporins C 40 (4 %. Conclusion (NICU 151 51 1,5 20 202 100 00 1,0 52. 5 (52 78. (78 4 ( 15 1, 10 0 (5 (7