Successful recall of a contextual memory requires reactivating ensembles of hippocampal cells that were allocated during memory formation. Altering the ratio of excitation-to-inhibition (E/I) during memory retrieval can bias cell participation in an ensemble and hinder memory recall. In the case of Rett syndrome (RTT), a neurological disorder with severe learning and memory deficits, the E/I balance is altered, but the source of this imbalance is unknown. Using in vivo imaging during an associative memory task, we show that during long-term memory retrieval, RTT CA1 cells poorly distinguish mnemonic context and form larger ensembles than wild-type mouse cells. Simultaneous multiple whole-cell recordings revealed that mutant somatostatin expressing interneurons (SOM) are poorly recruited by CA1 pyramidal cells and are less active during long-term memory retrieval in vivo. Chemogenetic manipulation revealed that reduced SOM activity underlies poor long-term memory recall. Our findings reveal a disrupted recurrent CA1 circuit contributing to RTT memory impairment. [Display omitted] • A mouse model of Rett syndrome (RTT) has impaired long-term contextual memory recall • Long-term recall recruits larger and more correlated ensembles of CA1 cells in RTT • OLM cells lacking MeCP2 are poorly recruited by CA1 pyramidal cells in RTT • Enhancing the activity of OLM cells restores long-term memory recall in RTT mice He et al. describe behavioral and CA1 activity dysfunctions during the long-term recall of a contextual memory in a Rett syndrome mouse model featuring heterozygous Mecp2 expression. The altered behavior and activity correlate with poor recruitment of inhibition from MeCP2-negative OLM cells. Enhancing this inhibition restores long-term memory recall. [ABSTRACT FROM AUTHOR]