Alzheimer’s disease (AD) is a progressive age-associated brain disorder in which deficits in episodic memory function are among the first cognitive symptoms observed. Clinical findings indicate that AD patients are more susceptible to anesthesia-induced postoperative cognitive dysfunction, which is in line with the well-known fact that general anesthesia is more detrimental in the two extreme age groups, neonates/infants and the elderly. Alfaxalone (ALX) is the synthetic analog of allopregnanolone. It is currently in use only in veterinary practice as a fast-acting anesthetic with a high therapeutic index. Recent studies report its numerous neuroprotective effects and, importantly, the absence of neurotoxic effects on the developing rat brain. The present study aims to examine the effects of ALX on AD-like brain and AD-related cognitive dysfunction, using novel mouse model of AD, the APPNL-G-F knock-in (KI) mice provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. The 9-month-old male KI mice and their non-KI littermates were treated with an anesthetic dose of ALX (40 mg/kg; s.c., 1/w) for four weeks, and subsequently tested using Open Field Test and Novel Object Recognition Test with Object Relocation. The behavioral assessments revealed no significant changes in ALX-treated animals compared to the controls, or between the genotypes, for all parameters analyzed: motor activity, latency to approach the novel object, number of approaches, time spent exploring the object, and the recognition index. Overall, our findings imply that an anesthetic dose of ALX does not affect mnemonic brain functions in male APPNL-G-F mice.