Although 2 or more sleep onset rapid eye movement (REM) periods (2omSOREMPs) on a Multiple Sleep Latency Test (MSLT) raise the possibility of narcolepsy, patients with obstructive sleep apnea (OSA) also can have 2omSOREMPs, which may then cause diagnostic uncertainty. To explore what features among OSA patients predict 2omSOREMPs on an MSLT that follows nocturnal polysomnography, we reviewed data from 1,145 consecutively studied patients suspected or confirmed to have OSA rather than narcolepsy. Overall, 4.7% of the subjects had 2omSOREMPs. Variables that were independently predictive of 2omSOREMPs in logistic regression models included male gender (OR = 4.4, 95% CI = 1.9 to 12.7), a 5-min decrease in the MSLT-derived mean sleep latency (OR = 1.9, 95% CI = 1.3 to 2.8), a 90-min decrease in nocturnal latency to REM sleep (OR = 1.6, 95% CI = 1.1 to 2.5), and a 15-unit decrease in minimal recorded oxygen saturation (OR = 1.6, 95% CI = 1.3 to 2.0). We conclude that among patients suspected or confirmed to have OSA, one or more of these four variables-male sex, sleepiness, nocturnal REM sleep latency, and extent of oxygen desaturation-could reflect neurophysiological mechanisms responsible for 2omSOREMPs. Consideration of these variables, and especially gender, may be useful in clinical practice when 2omSOREMPs are found unexpectedly.