Fatigue-related road accident is now being an alarming issue in many countries, including Malaysia. This paper developed a driving fatigue strain index (DFSI) by using fuzzy logic approach to analyze the impairment risk levels of three significant cognitive skills that influence driving fatigue, namely (i) alertness,(ii) attention and (ii) decision making. A human-related factor which is oxygen saturation was also analysed. The DFSI projected an advance warning method to alert users through a systematic analysis, proposing a solution to avoid road crashes. The fuzzy logic is developed by building fuzzy inference system (FIS) through Fuzzy Logic Toolbox function by MATLAB software. The input variables (alertness, attention, decision making and oxygen saturation) and an output variable (DFSI) were first divided into fuzzy sets by using fuzzy logic designer interface. Next, the shapes of all the membership functions associated with the input and output variables were developed by using membership function (MF) editor. IF-THEN rules statement was then employed to formulate the conditional statements of membership functions. Finally, the rule viewer interpreted all the rules and illustrated how the shape of particular membership functions influenced the overall results, eventually, reaching the DFSI degree. The DFSI degree is then defined as ‘safe’,‘slightly unsafe’and unsafe. The DFSI degree is expected to be useful to quantify the current driver’s condition in terms of cognitive abilities. Hence, this provides an advance warning to the driver to help avoid accidents and to ensure everyone reaches their destination without harm.