Inland water is very susceptible to the input of pollutants. However, little is known about the occurrence of antibiotics in inland lakes. In this study, a total of 83 target antibiotics were quantified in water and sediment samples collected from the Qinghai Lake, the largest inland lake of China located on the northeast of Qinghai-Tibet plateau, and its inflowing rivers. The results showed that 27 and 25 antibiotics were detected in water and sediments, respectively, with the summed concentrations (SUM) of 1.14-17.3 ng/L and 0.72-8.31 ng/g. Compared with the input rivers, significantly higher levels of sulfonamides (SAs), quinolones (QNs), polyethers (PEs), and SUM in water samples were observed in Qinghai Lake water. The average proportions of SAs (50.9-52.7%) and QNs (22.0-28.3%) in Qinghai Lake water nearly doubled compared to those in input rivers. An enrichment factor (EF) was proposed to reveal the enrichment degree of antibiotics in Qinghai Lake compared to its input river water. Sulfaguanidine (SGD), flumequine (FLU), and nalidixic acid (NDA) were enriched in Qinghai Lake up to several ten times based on the calculated EF values, due to their persistence in such a cold saline lake. Risk assessment showed that most antibiotics except anhydrochlortetracycline (ACTC) had insignificant risks to aquatic organisms and antibiotic resistance selection in Qinghai Lake water. This study was the first to reveal the enrichment of antibiotics in Qinghai Lake water, and suggests the urgent need to investigate the possible long-term enrichment and environmental risks of antibiotics in inland lakes.