Objectives To investigate whether loneliness and social isolation could independently predict subsequent risk of cognitive impairment in Chinese oldest old, and to examine possible gender differences. Methods The sample included 2,732 older adults aged 80 years and above with intact cognitive function from the Chinese Longitudinal Healthy Longevity Survey 2002-2018 waves, with an average follow-up of 4.24 years. Loneliness was measured by a single-item question about how often the participant felt lonely. Social isolation was defined by marital status, frequent visits by family members, and social activity engagement. Cognitive impairment was defined based on Mini-Mental State Examination scores. Results Cox regression showed that social isolation independently predicted a higher risk of developing cognitive impairment at follow-up (HR = 1.14, 95% CI [1.03, 1.27], p = 0.014). Importantly, although there was no main effect of loneliness, a significant interaction between gender and loneliness (p = 0.013) suggested that increased loneliness was associated with a higher risk of developing cognitive impairment for men but not for women. Conclusion To prevent cognitive impairment and promote healthy longevity, socially isolated adults in their oldest old age should receive more attention, and men who often feel lonely should be offered with more emotional support.