Background: To investigate if specific sow and piglet behavioral characteristics could be used diagnostically, this case-cohort study of the behavior of sows and piglets during the periparturient period (from 24 h before the birth of first piglet to 24 h after the birth of last piglet) was conducted. Data included 32 sows diagnosed with PDS (PDS+) vs. 37 healthy matched controls (PDS−) and their litters. Results: A significant change from active behavior with many postural changes to a more passive behavior was noted in connection with parturition. Sow nesting behavior was less frequent in PDS+ sows compared to PDS− sows during (p = 0.04) and after parturition (p = 0.0004). No difference was found between PDS+ and PDS− in the number of postural changes, interval from last time standing to the birth of the first piglet, interval from last time eating/drinking to the birth of the first piglet, interval from the birth of the first piglet to the sow standing after farrowing, interval from the birth of the last piglet until eating/drinking, occurrence of bar biting, or frequency or duration of eating/drinking during the observation period. Piglets of PDS+ sows stayed outside the creep areas more often than piglets of PDS− sows (p < 0.0001), but there was no difference in the mean number of piglets observed massaging the udder every 10 min. Conclusion: These results confirm that sow behavior changes from active before parturition to more passive after parturition. Being diagnosed with PDS affected the periparturient behavior of sows as well as their piglets. The observed reduction in nesting behavior in PDS+ sows may suggest that a highly motivated piglet-oriented behavior was affected. However, classical sickness behaviors like lethargy and passivity seem to be poor markers for PDS.