What's the matter? You look sad. 你怎么了?看着这么伤心。

What's wrong/Is anything wrong? 出什么事了？

Is something bothering you? 遇到什么麻烦了吗？

Are you okay/Are you all right? 你没事吧？

What's going on? 到底怎么回事?

Is something on your mind? 有什么烦心事吗？

What are you worried about? 你担心什么?

You look serious. 你怎么那么严肃。

You look grave. 你今天看上去很悲伤。

You look sad today. 你今天怎么满脸的不高兴。

You don't look very happy today. 你今天看着好像不太高兴啊。

Why are you so glum¹? 你怎么闷闷不乐的呀?

Why the long face? 你怎么拉着脸啊？

You look exhausted/tired/worn-out. 你看着很疲惫的样子。

You need a break. 你需要喘口气。

Something is wrong with you today. 你今天有点儿不大对劲。

You're not yourself today. 你今天有点儿不大对劲。

You seem different today. 你今天有点儿不大对劲。