Abstract Background After 2008 global economic crisis, Italian governments progressively reduced public healthcare financing. Describing the time trend of health outcomes and health expenditure may be helpful for policy makers during the resources’ allocation decision making process. The aim of this paper is to analyze the trend of mortality and health spending in Italy and to investigate their correlation in consideration of the funding constraints experienced by the Italian national health system (SSN). Methods We conducted a 20-year time-series study. Secondary data has been extracted from a national, institution based and publicly accessible retrospective database periodically released by the Italian Institute of Statistics. Age standardized all-cause mortality rate (MR) and health spending (Directly Provided Services - DPS, Agreed-Upon Services - TAUS, and private expenditure) were reviewed. Time trend analysis (1995–2014) through OLS and Multilayer Feed-forward Neural Networks (MFNN) models to forecast mortality and spending trend was performed. The association between healthcare expenditure and MR was analyzed through a fixed effect regression model. We then repeated MFNN time trend forecasting analyses on mortality by adding the spending item resulted significantly related with MR in the fixed effect analyses. Results DPS and TAUS decreased since 2011. There was a mismatch in mortality rates between real and predicted values. DPS resulted significantly associated to mortality (p