Embodiments herein include implantable medical systems, devices and methods including chemical sensors. In an embodiment, an implantable medical device system includes a chemical sensor; a fluid state sensor such as a posture sensor; an activity sensor; and/or a respiration sensor. The implantable medical device system can further include normalization circuitry receiving data from the chemical sensor and the fluid state sensor and normalizing the chemical sensor data based on data from the fluid state sensor. In an embodiment, a method of operating an implantable medical device system is included. The method can include measuring the amount of a chemical analyte using a chemical sensor, measuring the fluid status in a patient using a fluid state sensor, and normalizing the measured amount of the chemical analyte as indicated by the chemical sensor using normalization circuitry based on data from the fluid state sensor. Other embodiments are also included herein.