The purpose of this work is to develop a new Key Performance Indicator (KPI) that can quantify the cost of Six Big Losses developed by Nakajima and implements it in a Cyber Physical System (CPS), achieving a real-time monitorization of the KPI. This paper follows the methodology explained below. A cost model has been used to accurately develop this indicator together with the Six Big Losses description. At the same time, the machine tool has been integrated into a CPS, enhancing the real-time data acquisition, using the Industry 4.0 technologies. Once the KPI has been defined, we have developed the software that can turn these real-time data into relevant information (using Python) through the calculation of our indicator. Finally, we have carried out a case of study showing our new KPI results and comparing them to other indicators related with the Six Big Losses but in different dimensions. As a result, our research quantifies economically the Six Big Losses, enhances the detection of the bigger ones to improve them, and enlightens the importance of paying attention to different dimensions, mainly, the productive, sustainable, and economic at the same time.