The role of sleep on memory consolidation is thought to involve experience-dependent changes in spindle oscillations and protein phosphorylation, but how these phenomena are related remains poorly understood. To gain insight into this relationship, we used electrophysiological recordings and quantitative phosphoproteomic analysis to assess spindle oscillations and phosphoprotein levels in the hippocampus (HP) and primary somatosensory cortex (S1) of adult male rats recorded across the sleep cycle. Animals were surgically implanted with multielectrode probes and after recovery were exposed or unexposed to novel objects (+ and – groups, respectively). HP and S1 samples were obtained after periods rich in either slow-wave sleep (SWS) or rapid-eye-movement sleep. Bottom-up shotgun mass spectrometry in a two-dimensional liquid chromatography-tandem mass spectrometry setup (MSE mode with label-free quantification) showed that the proteomes differed in the numbers of phosphoproteins identified by phosphoryl modification STY tags, with a total of 337 validated phosphoproteins identified in S1 and 198 in the HP. A comparison of the phosphoproteomic profiles of the treatments and regions (SWS+ versus SWS-, REM+ versus REM-, REM+ versus SWS+ and REM- versus SWS-), using clustering analysis of the significantly identified phosphoproteins, found that 51 phosphoproteins from S1 were sufficient to separate the four experimental conditions, while 37 phosphoproteins from the HP could only partially separate the groups. Fold change analysis identified 90 significantly modulated phosphoproteins related to synaptic function, actin-microtubule regulation, DNA-RNA binding, proteases-phosphatases-kinases and other regulatory functions, including CaMKII and MAPK. In both the HP and S1, nearly one third of the clustering-relevant phosphoproteins had levels significantly correlated with the abundance of spindle oscillations pooled across the transition from SWS to REM. In S1, phosphorylated Reelin was upregulated during REM compared to SWS, in proportion to the number of spindle oscillations during the transition from SWS to REM. In the HP, a voltage-gated calcium channel subunit (Cacna2d1) was down-regulated during SWS+ compared to REM+, in proportion to spindle counts. Since spindles facilitate calcium entry through the opening of voltage-dependent calcium channels, Cacna2d1 down-regulation may lead to a hippocampus-specific, REM-dependent downregulation of synaptic plasticity after exposure to novel objects. The results point to major experience-dependent differences between HP and S1 in phosphoproteomic regulation across the sleep cycle, with potential implications for memory corticalization.