BACKGROUND: Learning burnout, which is a negative state of learning and seriously reduces learning engagement, has become more prevalent in online instruction. Especially during the COVID-19, loneliness during the online learning has attracted a great deal of attention from researchers, who have found that it exacerbates the risk of social media addiction and increase rates of depression. However, the relationship between loneliness and academic burnout in online formal learning has not been well explored in previous studies. Therefore, the present study explores whether and to what extent loneliness suffered by students in online formal learning triggers academic burnout, and whether there are factors that buffer the effects of loneliness on academic burnout, thus filling the gap in the current research. METHODS: Using self-reported data from 618 college students from central China through convenience sampling, this paper used hierarchical linear regression to test the direct effect of loneliness on learning burnout. Three moderation was conducted to reveal the role that 3 interesting factors (academic buoyancy, social presence and online learning duration) play in the relationship between loneliness and online learning burnout. RESULTS: We found that loneliness triggered burnout in online learning, while social presence relieve burnout. However, academic buoyancy, social presence and online learning duration cannot buffer against the online learning burnout caused by loneliness. CONCLUSIONS: Loneliness in online learning should not be ignored, as it can cause different degrees of learning burnout, no matter whether learners have high or low academic buoyancy and social presence. Future research should continue to investigate how to alleviate loneliness in online learning.