<p>Exposure to novelty can enhance memory performance through behavioural tagging, whereby novel experiences strengthen temporally proximate memories. Whilst consistently demonstrated in rodents, human studies have yielded mixed results, possibly due to inadequate novelty manipulations and/or insufficient hippocampal engagement during encoding. Here, we investigated whether exploration of a novel, unpredictable, immersive virtual reality retroactively enhanced spatial memory in humans. Thirty-six participants completed a two-day experiment involving spatial object-location learning in custom mazes, with encoding strength manipulated through repetition, to create initially weak and strong encoding conditions. Following encoding, participants explored either familiar (predictable city) or novel (multi-site outer-space with unpredictable teleportation) virtual environments. Memory was assessed through spatial accuracy metrics and cued recall. We found a retroactive memory enhancement following novel environment exploration, specifically when novelty occurred on Day 2. This enhancement was evident across spatial memory measures and cued recall, but did not interact with encoding strength. Our results demonstrate that retroactive behavioural tagging effects can be elicited in humans using spatial memory tasks paired with immersive novelty experiences, provided participants have appropriate reference points for novelty evaluation. These findings highlight the importance of investigating behavioural tagging using manipulations that emulate those studied in rodents.</p>