Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca²⁺ oscillations in the mouse somatosensory cortex. The intracellular Ca²⁺ changes of SR101 labeled astrocytes and the SD-related arteriole diameter variations were simultaneously visualized by multiphoton microscopy in anesthetized mice. Post-SD astrocyte Ca²⁺ oscillations were identified as Ca²⁺ events non-synchronized among astrocytes in the field of view. Ca²⁺ oscillations occurred minutes after the Ca²⁺ wave of SD. Furthermore, fewer astrocytes were involved in Ca²⁺ oscillations at a given time, compared to Ca²⁺ waves, engaging all astrocytes in the field of view simultaneously. Finally, our data confirm that astrocyte Ca²⁺ waves coincide with arteriolar constriction, while post-SD Ca²⁺ oscillations occur with the peak of the SD-related vasodilation. This is the first in vivo study to present the post-SD astrocyte Ca²⁺ oscillations. Our results provide novel insight into the spatio-temporal correlation between glial reactivity and cerebral arteriole diameter changes behind the SD wavefront.