Cyber-Physical Systems (CPS) combine computational, communication, sensory and control capabilities to monitor and regulate physical domain processes. CPSs are becoming increasingly networked with the cyber world, opening access to communication with control rooms, command and control stations, other computer based systems, or even the Internet. Examples of cyber-physical systems include transportation networks, Unmanned Aerial Vehicle Systems (UAV's), nuclear power generation, electric power distribution networks, water and gas distribution networks, and advanced communication systems. In all cases, current technology has introduced the capability of integrating information from numerous instrumentation and control systems and transmitting needed information to operations personnel in a timely manner. While the application of perimeter security technologies has been utilized to help manage the possibility of cyber attackers exploiting highly automated cyber physical systems, the rate of successful attacks against critical infrastructures continues to be problematic and increasing [1]. Furthermore, the trend in adversarial attacks is moving toward well-formed coordinated multi-vector attacks that compromise the system in such a way that detection and identification is challenging for perimeter security solutions and human monitoring. This research effort constructed a methodology to defend against stealthy, low probability of detection, and high impact cyber-attacks on CPS. The goal is to increase the level of difficulty to perform a stealthy attack by improving the probability of detection, isolation and limiting the impact of an attack. The study uses the example of a UAV navigation system comprising of a redundant set of INS and GPS units solving the problem posed by Kwon et al [2] that there exist false injection attacks that evade fault detection techniques, allowing the adversary to deviate an aircraft. The examined architecture is comprised of a diverse sensory architecture within the CPS, avoiding supply chain vulnerabilities, and provides several possible trustworthy references. Expanding from a system with multiple components, a similarity measurement between INSs and GPSs is developed leveraging their unique characteristics and relationship. Assuming that an adversary is restricted to attacking a singular navigation component, the method is able to detect and isolate persistent cyber-attack for a large enough deviation.