The basic functions of an autonomous vehicle typically involve navigating from one point to another in the world by following a reference path and analyzing the traversability along this path to avoid potential obstacles. What happens when the vehicle is subject to uncertainties in its localization? All its capabilities, whether path following or obstacle avoidance, are affected by this uncertainty, and stopping the vehicle becomes the safest solution. In this work, we propose a framework that optimally combines path following and obstacle avoidance while keeping these two objectives independent, ensuring that the limitations of one do not affect the other. Absolute localization uncertainty only has an impact on path following, and in no way affects obstacle avoidance, which is performed in the robot’s local reference frame. Therefore, it is possible to navigate with or without prior information, without being affected by position uncertainty during obstacle avoidance maneuvers. We conducted tests on an EZ10 shuttle in the PAVIN experimental platform to validate our approach. These experimental results show that our approach achieves satisfactory performance, making it a promising solution for collision-free navigation applications for mobile robots even when localization is not accurate.