Animals are exposed to lithium (Li+) in the natural environment as well as by contact with industrial sources and therapeutic treatments. Low levels of exposure over time and high volumes of acute levels can be harmful and even toxic. The following study examines the effect of high-volume acute levels of Li+ on sensory nerve function and nerve conduction. A proprioceptive nerve in the limbs of a marine crab (Callinectes sapidus) was used as a model to address the effects on stretch-activated channels (SACs) and evoked nerve conduction. The substitution of Li+ for Na+ in the bathing saline slowed nerve conduction rapidly; however, several minutes were required before the SACs in sensory endings were affected. The evoked compound action potential slowed in conduction and slightly decreased in amplitude, while the frequency of nerve activity with joint movement and chordotonal organ stretching significantly decreased. Both altered responses could be partially restored with the return of a Na+-containing saline. Long-term exposure to Li+ may alter the function of SACs in organisms related to proprioception and nerve conduction, but it remains to be investigated.