故事以高仓家三兄妹为中心而展开，高仓冠叶（木村昴 配音）、高仓晶马（木村良平 配音）兄弟俩和患有绝症的妹妹高仓阳毬（ 荒川美穂 配音）。
有妹控情结的高仓兄弟俩都非常珍视阳毬，然而医生却让他们做好随时失去妹妹的准备。这天兄妹三人一同去水族馆游玩，可是一转眼兄弟二人发现妹妹不见了，随后他们在围观人群中央发现倒地不醒的阳毬。抢救无效被宣布死亡的阳毬竟然在停尸房里醒过来了！惊讶无比的兄弟俩把妹妹接回家，不久后他们收到了一份奇怪的包裹，打开后竟然发现里面有三只谜样企鹅。这三只企鹅憨态可掬，除了他们，外人都看不见这些企鹅。这一切究竟是怎么回事，命运的齿轮又会如何转动？

As with its prequel, Zoku Natsume Yuujinchou is about Takashi Natsume, a boy who has had the ability to see youkai since he was young, and his bodyguard youkai Madara, nicknamed Nyanko-sensei. Natsume attempts to return names written in his "Book of Friends" (which he inherited from his grandmother Reiko) to youkai in his village. Throughout these adventures, he meets some youkai that are friendly, some that want to steal the Book, and some that want to kill him, as Natsume learns about himself and his relationship with these mysterious beings along the way.