Classical swine fever (CSF) caused by the CSF virus (CSFV) is one of the most important swine diseases, resulting in huge economic losses to the pig industry worldwide. Systematic vaccination is one of the most effective strategies for the prevention and control of this disease. Two main CSFV vaccines, the modified live vaccine (MLV) and the subunit E2 vaccine, are recommended. In Taiwan, CSF cases have not been reported since 2006, although systemic vaccination has been practiced for 70 years. Here, we examined the sero-dynamics of the piglets born from sows that received either the CSFV MLV or the E2 vaccine and investigated in the field the correlation between the porcine reproductive and respiratory syndrome virus (PRRSV) loads and levels of CSFV antibody. A total of 1398 serum samples from 42 PRRSV-positive farms were evaluated to determine the PRRSV loads by real-time PCR and to detect CSFV antibody levels by commercial ELISA. Upon comparing the two sow vaccination protocols (CSFV MLV vaccination at 4 weeks post-farrowing versus E2 vaccination at 4–5 weeks pre-farrowing), the lowest levels of CSFV antibody were found in piglets at 5–8 and 9–12 weeks of age for the MLV and E2 groups, respectively. Meanwhile, the appropriate time window for CSFV vaccination of offspring was at 5–8 and 9–12 weeks of age in the MLV and E2 groups, respectively. There was a very highly significant negative correlation between the PRRSV load and the level of CSFV antibody in the CSFV MLV vaccination group (P < 0.0001). The PRRSV detection rate in the pigs from the MLV group (27.78%) was significantly higher than that in pigs from the E2 group (21.32%) (P = 0.011). In addition, there was a significant difference (P = 0.019) in the PRRSV detection rate at 5–8 weeks of age between the MLV (42.15%) and E2 groups (29.79%). Our findings indicate that the vaccination of CSFV MLV in piglets during the PRRSV susceptibility period at 5–8 weeks of age may be overloading the piglet’s immune system and should be a critical concern for industrial pork production in the field.