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Pore-cave systems formed by karstification in the eogenetic stage of carbonate rocks provide abundant potential reservoir space for hydrocarbons. However, whether these dissolution pore-caves can become effective reservoir spaces during the later burial period, serving as the key to the success of hydrocarbon exploration. Therefore, it is important to explore the fluid activities and their alteration effects on eogenetic karst reservoirs during the later burial. Focusing on the Cambrian Longwangmiao Formation in the northwestern Sichuan Basin, this study systematically analyzed the formation of reservoir space in the eogenetic stage and the reworking of the system by fluids in the later stages, based on petrology, geochemistry, burial history, and tectonic evolution data. Results showed that many millimeters to several centimeters scale of pores and caves in the Longwangmiao Formation were produced by eogenetic karstification. These pore-caves underwent by two episodes of dolomite infilling in the shallow burial stage (D1) and in the Caledonian–Hercynian period (D2). Geochemical parameters indicate that D1 and D2 were both affected by meteoric water. In the early shallow burial stage, the dolomitic fluid was enriched in a relatively closed, reducing environment, whereas in the later stage, the fluid was affected by a relatively open oxidizing environment due to Caledonian–Hercynian fractures. Both D1 and D2 took place before the massive hydrocarbon migration from the Cambrian source rocks in the Middle Permian to those of the Middle Triassic. After the formation of the dissolution pore-caves, the precipitation from two episodes of dolomitic fluids led to the degradation of the Longwangmiao Formation carbonate reservoir space in the northwestern Sichuan Basin. In the southern part of the Shatan section-Well MS1, closed to the paleo-uplift of the central Sichuan Basin, where eogenetic karstification was superimposed by Caledonian–Hercynian supergene karstification, may be form effective reservoir and is a significant prospect for exploration. [ABSTRACT FROM AUTHOR]