Objectives This study identified distinct social isolation profiles among caregivers, each formed by varied combinations of social disconnectedness and loneliness, and examined if and how the profiles were associated with caregiver burden. Methods Latent class analysis and multivariable regression were applied to data from 266 caregivers of community-dwelling older Singaporeans with cognitive impairment. Results Two caregiver social isolation profiles were identified: strongly connected, not lonely (86%), and moderately connected, lonely (14%). Moderately connected and lonely caregivers tended to perceive a higher level of burden than strongly connected and not lonely caregivers. Moderately connected and lonely caregivers were also more likely to be burdened by their care recipients’ poor health than their connected and not lonely counterparts. Discussion Caregivers who feel “lonely in a crowd” are vulnerable to caregiving stress and burden. Tailored interventions, such as cognitive behavioral therapy, are needed to reduce the loneliness of moderately connected caregivers.