The amygdala and orbitofrontal cortex (OFC) are interconnected regions that serve as key nodes in brain circuits supporting social and affective behaviors. An important question that has come into focus is whether these regions also play a fundamental role in responding to novelty. One possibility is that these regions are important for discriminating novel from familiar stimuli. An alternative possibility is that these regions contribute to affective responses to stimuli in novelty-based tasks. For example, the amygdala and OFC could contribute to assessing novel stimuli as being threatening or previously selected stimuli as having reward value. The present study tested rhesus macaque monkeys with damage to the amygdala or OFC, along with sham-operated control monkeys, across six variants of novelty-based memory tasks. The results showed that monkeys with damage to the amygdala or OFC performed better overall than control monkeys across the tasks. The results indicated that neither region was essential for discriminating novel from familiar stimuli. Instead, the findings suggested that the improved performance observed in novelty-based tasks following damage to these regions was more likely attributable to influences on affect.