Study design: Prospective, double-blind, randomised, placebo-controlled, cross-over trial of nasal decongestion in tetraplegia. Objectives: Tetraplegia is complicated by severe, predominantly obstructive, sleep apnoea. First-line therapy for obstructive sleep apnoea is nasal continuous positive airway pressure, but this is poorly tolerated. High nasal resistance associated with unopposed parasympathetic activation of the upper airway contributes to poor adherence. This preliminary study tested whether reducing nasal decongestion improved sleep. Setting: Participants’ homes in Melbourne and Sydney, Australia. Methods: Two sleep studies were performed in participants’ homes separated by 1 week. Participants were given a nasal spray (0.5 mL of 5% phenylephrine or placebo) in random order and posterior nasal resistance measured immediately. Outcomes included sleep apnoea severity, perceived nasal congestion, sleep quality and oxygenation during sleep. Results: Twelve middle-aged (average (SD) 52 (12) years) overweight (body mass index 25.3 (6.7) kg/m2) men (C4-6, AIS A and B) participated. Nasal resistance was reduced following administration of phenylephrine (p = 0.02; mean between treatment group difference −5.20: 95% confidence interval −9.09, −1.32 cmH2O/L/s). No differences were observed in the apnoea hypopnoea index (p = 0.15; −6.37: −33.3, 20.6 events/h), total sleep time (p = 0.49; −1.33: −51.8, 49.1 min), REM sleep% (p = 0.50; 2.37: −5.6, 10.3), arousal index (p = 0.76; 1.15: −17.45, 19.75), 4% oxygen desaturation index (p = 0.88; 0.63: −23.5, 24.7 events/h), or the percentage of mouth breathing events (p = 0.4; −8.07: −29.2, 13.0) between treatments. The apnoea hypopnoea index did differ between groups, however, all except one participant had proportionally more hypopnoeas than apnoeas during sleep after decongestion. Conclusions: These preliminary data found that phenylephrine acutely reduced nasal resistance but did not significantly change sleep-disordered breathing severity.