This study presents a high-resolution record of δ15Nsed, which serves as a proxy for water column denitrification and oxygen minimum zone (OMZ) intensity, from the Soledad Basin in the Eastern Tropical North Pacific OMZ. The Soledad Basin δ15Nsed record is compared to the Pescadero Slope and Santa Barbara Basin (SBB) δ15Nsed records to gain insight into regional variations in the ETNP OMZ. During the Medieval Climate Anomaly (MCA; 950–1250 CE), Soledad Basin, Pescadero Slope, and SBB records exhibit coherent trends suggesting that there was general water column oxygenation stability. During the Little Ice Age (LIA; 1350–1850 CE), Soledad Basin and SBB showed a similar decreasing trend in δ15Nsed values while the Pescadero Slope δ15Nsed exhibited an increasing trend until values abruptly declined between 1740 and 1840 CE. We suggest that increased δ15Nsed variability and the different trends at the Pescadero Slope during the LIA are due to the influence of the North American monsoon (NAM), which can suppress upwelling when enhanced and result in OMZ contraction. The decoupling between the Soledad Basin, SBB, and the Pescadero Slope could also be due to the increased influence of enriched 15NO3− subarctic waters in the California Current System. Since each site is influenced by local productivity, basin morphology, and regional atmospheric and ocean circulation patterns, we suggest that assessing OMZ fluctuations from multiple sites provides a more comprehensive view of regional OMZ dynamics in response to climate variations.