The Mediterranean region is increasingly recognized as a climate change hotspot but is highly underrepresented in hydrological climate change studies. This study aims to investigate the climate change effects on the hydrology of Lakhmass catchment in Tunisia. Lakhmass catchment is a part of the Medium Valley of Medjerda in northwestern Tunisia that drains an area of 126 km². First, the Hydrologiska Byråns Vattenbalansavdelning light (HBV-light) model was calibrated and validated successfully at a daily time step to simulate discharge during the 1981–1986 period. The Nash Sutcliffe Efficiency and Percent bias (NSE, PBIAS) were (0.80, +2.0%) and (0.53, −9.5%) for calibration (September 1982–August 1984) and validation (September 1984–August 1986) periods, respectively. Second, HBV-light model was considered as a predictive tool to simulate discharge in a baseline period (1981–2009) and future projections using data (precipitation and temperature) from thirteen combinations of General Circulation Models (GCMs) and Regional Climatic Models (RCMs). We used two trajectories of Representative Concentration Pathways, RCP4.5 and RCP8.5, suggested by the Intergovernmental Panel on Climate Change (IPCC). Each RCP is divided into three projection periods: near-term (2010–2039), mid-term (2040–2069) and long-term (2070–2099). For both scenarios, a decrease in precipitation and discharge will be expected with an increase in air temperature and a reduction in precipitation with almost 5% for every +1 °C of global warming. By long-term (2070–2099) projection period, results suggested an increase in temperature with about 2.7 °C and 4 °C, and a decrease in precipitation of approximately 7.5% and 15% under RCP4.5 and RCP8.5, respectively. This will likely result in a reduction of discharge of 12.5% and 36.6% under RCP4.5 and RCP8.5, respectively. This situation calls for early climate change adaptation measures under a participatory approach, including multiple stakeholders and water users.