Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration and loss of motor neurons, resulting in severe muscle weakness and paralysis. The respiratory system is implicated in ALS, with patients experiencing sleep-disordered breathing and progressive respiratory muscle weakness, ultimately leading to respiratory muscle paralysis and failure. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. It remains to be determined whether muscle dysfunction in ALS is a consequence of motor unit degeneration subsequent to motor neuron loss, or whether there is a primary muscle disorder in ALS that contributes to muscle dysfunction, thereby disrupting neuromuscular junction physiology and contributing to muscle dysfunction. These views are broadly considered as “dying forward” (nerve to muscle) or “dying back” (muscle to nerve) phenomena. It is suggested that muscle impairment may exist early, before the onset of overt motor impairments in ALS mice and perhaps humans. Therefore, we hypothesize that upper airway muscle dysfunction presents early in ALS and precedes cranial motor neuron dysfunction. We aimed to examine upper airway and diaphragm muscle function in young (48-49 days) pre-symptomatic ALS mice.  We examined ex vivo muscle contractile function of sternohyoid (a representative pharyngeal dilator) and diaphragm muscles for wild-type (n=12) and ALS (n=12) mice. Muscle preparations were attached to a dual-mode lever transducer system and studied in a water-jacketed muscle bath containing Krebs solution at 35oC aerated with 95%O2/5%CO2. Isometric contractions were performed to examine force-generating capacity. Isotonic contractions were performed at 0% load to examine maximum shortening (Smax) and shortening velocity (Vmax) and at 50% load to examine maximum work (Wmax) and power (Pmax) output. Values are expressed as mean ± S.D. Data were statistically compared using unpaired Student’s t test, Mann Whitney test or two-way ANOVA with Bonferroni post hoc test. P<0.05 was considered statistically significant.  Sternohyoid muscle tetanic force was significantly reduced in ALS mice compared to wild-type. For the force-frequency relationship, specific force was significantly reduced at 100-150 Hz. Smax, Vmax, Wmax and Pmax were all significantly reduced in ALS sternohyoid muscle compared to wild-type. Conversely, for diaphragm muscle, there was no significant difference in force production in ALS mice compared to wild-type. Smax, Vmax, Wmax and Pmax were also equivalent for ALS and wild-type diaphragm muscle preparations. These data demonstrate sternohyoid muscle weakness (evidenced by reduced specific force and power output) in young pre-symptomatic ALS mice. Diaphragm muscle function was unaffected in pre-symptomatic ALS mice. Our study indicates that upper airway muscle dysfunction may be a prodromal signature of ALS, with potential implications for the control of upper airway patency in ALS and other neurodegenerative diseases. Current studies seek to examine brainstem and spinal cord motor neuron pools to compare motor and muscle changes in young ALS mice.