Cold stress is one of the major factors limiting rice (Oryza sativa L.) productivity and yield. Two rice cultivars were chosen for this study: a japonica rice, ‘Gerde’, and an indica rice, ‘Shiroodi’, representing tolerant and sensitive cultivars, respectively. In this work, the early physiological and molecular responses of these two cultivars to 4°C cold stress were investigated. We found that cold stress caused a significant decrease in the content of chlorophyll a, chlorophyll b, and carotenoids in both rice cultivars. However, the photosynthetic pigment content in the Shiroodi cultivar decreased to a greater extent, indicating its limited genetic capacity to protect its photosynthetic machinery. During cold stress, the amounts of hydrogen peroxide and malondialdehyde produced by the Shiroodi cultivar were significantly higher than those in Gerde, suggesting a lower capacity of Shiroodi to scavenge reactive oxygen species. The higher level of beta-glucosidase gene expression in the final hours of cold treatment in the Gerde cultivar indicates the involvement of this enzyme in elevating cellular levels of active abscisic acid. Moreover, the significant increase observed in the transcript level of phenylalanine-ammonia-lyase in Gerde indicates the induction of defense responses related to the phenylpropanoid pathway. Altogether, one can conclude that the higher cold tolerance of the Gerde cultivar is multifaceted, involving various factors such as its ability to protect its photosynthetic machinery, its greater capacity for cell protection against oxidative stress, and the expression modulation of genes involved in abscisic acid metabolism and secondary metabolism.