After chronic C2 spinal hemisection (C2HS), exposure to intermittent hypoxia (IH) evokes a persistent increase in phrenic output recorded ipsilateral to the injury (i.e., phrenic long-term facilitation, LTF; Golder and Mitchell, J. Neurosci. 25:2925-32, 2005). However, unilateral spinal cord injury induces compensatory increases in contralateral motoneuron activity that may reduce their capacity for further plasticity (i.e., a "ceiling effect"). We hypothesized that after chronic C2HS, LTF would be reduced in contralateral (vs. ipsilateral) phrenic output. Bilateral phrenic activity was recorded in three groups of anesthetized, paralyzed, vagotomized, and ventilated rats: uninjured, and 4 or 8 weeks following histologically verified C2HS. Baseline (BL) phrenic activity was established during normoxia and rats were then exposed to IH (5 x 3 min isocapnic hypoxia, 13-14% O2) followed by isocapnic normoxia; LTF was assessed 60-min post-IH. Uninjured animals showed an increase in inspiratory burst amplitude that was similar in the left (44 +/- 11%BL) and right phrenic nerves (39 +/- 13%BL). However, similar burst amplitude LTF did not occur in phrenic output recorded contralateral to C2HS at 4 (-10 +/- 7% BL) or 8 weeks post-C2HS (4 +/- 5% BL). In contrast, LTF of ipsilateral phrenic amplitude occurred at both 4 (44 +/- 11% BL) and 8 weeks post-C2HS (129 +/- 30% BL, P < 0.05). A persistent increase in phrenic burst frequency after IH (i.e., "frequency LTF") was observed in control (+9 +/- 3 burst/min, P < 0.05), but not C2HS rats. We conclude that compensatory responses to unilateral cervical spinal cord injury prevent the expression of LTF in contralateral phrenic motoneurons.