Background Salmonellosis remains the second most common zoonosis in the European Union despite a long-term decreasing trend. However, this trend has been reported to have stagnated in recent years, particularly for Salmonella enterica serotype Enteritidis (SE). Aim To describe temporal changes in the incidence of SE human infections, and in its associated factors between 2006 and 2019. In addition, we aim to determine which factors influenced the stagnated trend seen in recent years. Methods Data on culture-confirmed SE human infections from national surveillance registries in the Netherlands and Belgium between 2006 and 2019 were analysed using multivariable negative-binomial regression models with restricted cubic splines. Results SE incidence was significantly higher in summer and autumn than winter, in persons aged 0–4 years and 5–14 years than in persons ≥ 60 years, and increased with increasing proportions of travel-related and resistant SE infections. SE incidence decreased significantly in both countries until 2015, followed by an increasing trend, which was particularly pronounced in the Netherlands. Potential SE outbreaks in both countries and invasive infections in the Netherlands also increased after 2015. Conclusion The increase in potential outbreaks and invasive infections since 2015 may partially explain the observed reversal of the decreasing trend. While these results provide insights into the possible causes of this trend reversal, attention should also be given to factors known to influence SE epidemiology at primary (animal) production and pathogen genomic levels.