In this paper, the performance of a solar still equipped with a heat exchanger using nanofluids has been studied both experimentally and theoretically through three key parameters, i.e., freshwater yield, energy efficiency and exergy efficiency. First, experiments are performed on a set-up, which is mainly composed of two flat plate solar collectors connected in series, and a solar still equipped with a heat exchanger. After heated in the collectors, the nanofluid enters the heat exchanger installed in the solar still basin to exchange heat with brackish water. The research question is to know how much the effect of nanofluids on the evaporation rate inside the solar desalination system is. The experiments are conducted for different nanoparticle volume fractions, two sizes of nanoparticles (7 and 40 nm), two depths of water in the solar still basin (4 and 8 cm), and three mass flow rates of nanofluids during various weather conditions. It is found that the weather conditions (mainly the sun radiation intensity) have a dominant influence on the solar still performance. To discover the effects of nanofluids, a mathematical model is developed and validated by experimental data at given weather conditions. The results reveal that using the heat exchanger at temperatures lower than 60 °C is not advantageous and the corresponding yield is smaller than that of solar still without the heat exchanger; although in such a case, using nanofluids as the working fluid in the heat exchanger can enhance the performance indices about 10%. At higher temperatures (e.g. 70 °C), the use of heat exchanger is beneficial; however, using nanofluids instead of water can augment the performance indices marginally i.e. just around 1%. In addition, it is found that in high temperatures using SiO2/water nanofluids, which have a lower effective thermal conductivity than that of Cu/water nanofluids, provides higher performance indices.